This study will evaluate the efficacy, safety and patient reported outcomes of chidamide 20 mg biw PO day1-14 and rituximab 375 mg/m2 IV given on day 1 and methotrexate 3.5g/m2 IV given on day 2 of every 21-day cycle for 6 cycles in untreated patients with primary central nervous system lymphoma.

The primary study endpoint will be complete response (CR) rate as assessed by the investigator. The hypothesis is previously untreated patients with primary central nervous system lymphoma could achieve a CR rate of 80% with C-R-HDMTX.

Inclusion Criteria:

1. ECOG Performance Status of 0, 1, or 2

2. Previously untreated patients with primary central nervous system lymphoma with pathologically confirm

3. At least one bi-dimensionally measurable lesion, defined as >1.0 cm in its longest dimension as measured by MRI

4. Signed written Informed Consent Form

5. hematologic function,defined as follows:

   • Hemoglobin ³ 9.0 g/dL without packed RBC transfusion during 14 days before first treatment
   • ANC ³ 1,000/µL
   • Platelet count ³ 80,000/µL

6. Adequate liver and kidney function function,defined as follows:

Serum AST and ALT≤ 2.5 *ULN ，Total bilirubin ≤ 1.5 * ULN Serum creatinine clearance ≥ 50 mL/min (using Cockcroft-Gault formula)

Exclusion Criteria:

1. Evidence of extracranial involvement (such as testis and breast) and secondary CNS involvement
2. Evidence of pleural fluid, ascites and pericardial effusion
3. History or presence of prolonged QTc interval in ECG, QTc interval>470ms in female and >450ms in male
4. History of other malignancy in 5 years
5. Positive test results for hepatitis C, HIV and RPR.
6. Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology) Patients with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is less than 10E4 at the time of screening.
7. Pregnancy or lactation or intending to become pregnant during study
8. Prior organ transplantation
9. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection at study enrollment or significant infections within 2 weeks before the start of Cycle 1.
10. Evidence of significant, uncontrolled, epilepsy