In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen （Methotrexate 3.5 g/m2, d1; Rituximab 375 mg/m2, d0）and escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively respectively on day 1,8,15,22 for 28-days cycle.~The phase 2 expansion at the recommended dose level based on phase 1b trial. The total 6 cycles, 28 days per cycle . And, Subjects participating in the study will undergo a screening period（up to 21days）, a treatment period, and a follow-up period. The screening period is a maximum of 21 days before treatment period, And will be followed by 6 cycles of combination treatment（28 days per cycle）.~partial remission(PR) patients after induction treatment will continue ATG-010 maintenance up to 1 year or until disease progression, intolerable toxicity, death.
This is a single-arm and open-label study to explore X+MTX+Ritu (ATG-010, Methotrexate, Rituximab) regimen in Relapse refractory PCNSL patients. Approximately 30 patients will be enrolled in the study. In dose escalation phase, patients with Relapse refractory PCNSL will be treated with X+MTX+Ritu regimen and escalating doses of oral ATG-010 weekly in a 3+3 design. Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.