This is a prospective, multicenter, single-arm, open Phase Ib/II clinical study to explore the safety and efficacy of pomadomide in combination with rituximab and methotrexate (RPM) in newly diagnosed primary central nervous system lymphoma (PCNSL) subjects. The Phase I study is a dose escalation study, in which rituximab and methotrexate are fixed doses, and pomadomide is set into 3 dose groups: 3mg/d, 4mg/d and 5mg/d. In strict accordance with the "3+3" dose escalation principle, 3-6 subjects are to be recruited in each dose group, and each subject is to be observed for 1 cycle after treatment to determine MTD. Phase II study: RP2D is planned to be determined based on the Phase Ib study, with an additional 25 active participants enrolled to further evaluate efficacy and safety. Subjects with initial treatment of PCNSL who met the inclusion/exclusion criteria were screened, and after signing the informed consent letter, they received 4 courses of PRM regimen. The patients achieving CR or PR were consolidated by autologous transplantation consolidation regimen or the original regimen for 2 courses, and then were given pomadomide maintenance therapy for 12 cycles. Follow-ups should be taken up to the first 3 years.
Histopathologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL).
The lesions were confined to the central nervous system, including the brain, spinal cord, eyes and meninges.
Through physical examination, imaging examination (including CT, MRI, PET-CT, etc.) and bone marrow puncture examination, it was confirmed that no parts other than the central nervous system were involved.
Patients who have not previously received chemotherapy or radiotherapy (except those with dexamethasone less than 10mg/ day (or equivalent dose) and duration less than 5 days).
Have systemic lymphoma disease.
Previous systemic or local treatment such as chemotherapy and/or radiotherapy and/or hematopoietic stem cell transplantation.
Previous or concurrent history of other malignant tumors requiring active therapy.
Chronic or currently active infectious diseases requiring systemic antibiotic, antifungal, or antiviral treatment (except EBV infections).
Single group
Pomalidomide
Drug3-5mg d1-d14 for 4-6 cycles, every 21 days as induction/consolidation chemotherapy, Then 3-5mg d1-d14 for 12 cycles, every 28 days as maintenance treatment.
Rituximab
Drug375mg/m2 intravenous infusion d1, every 3 weeks for 1 cycle, 4-6 cycles will be prescribed.
Methotrexate
Drug3.5g/m2 intravenous infusion for 4 hours in d1, every 21 days for 1 cycle, 4-6 cycles will be prescribed.
MTD
MTD of pomalidomide when given in combination with rituximab and methotrexate determined by dose-limiting toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Objective response rate(ORR)
The objective response rate is defined as the proportion of patients with a response of complete response(CR) or partial response(PR).
Progression free survival
From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years
Overall survival
From date of patients sign informed consent until the date of progression or death or the date of last follow-up time, whichever came first, assessed up to 3 years
pomalidomide levels in the CNS
Based on pomalidomide levels in CSF at different time points
pomalidomide levels in the Blood
Based on pomalidomide levels in blood at different time points
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