r2-mtx with lenalidomide maintenance in newly-diagnosed pcnsl：a multicenter phase ib/ii stuty

Conditions: Primary Central Nervous System Lymphoma

Summary: this is a multicenter prospective single arm phase ib/ii study, and the purpose of this study is to evaluate the safety and efficiency of r2-mtx regimen (rituximab \& lenalidomide \& methotrexate) combined with lenalidomide maintenance in newly-diagnosed primary central nervous system lymphoma. 2-year progression free survival (pfs) of the cohort is the primary endpoint.

there are 2 section of this trial. step1 is a phase ib study.the patients will be treated with r2-mtx regimen （rituximab 375mg/m2 iv d0, methotrexate 3.5g/m2 civ d1, lenalidomide 15-25mg d1-14, 21 days per cycle) as induction regimen.the dose of rituximab and methotrexate is fixed dose. this is a 3+3 design ib phase dose-escalation study to determined the maximum tolerated dose(mtd) of lenalidomide dose in combined regimen. 3 levels of lenalidomide dose will be investigated, 15mg, 20mg and 25mg. if the dlt is not found, the dose of 25mg qd will be used for phase ii trial. \[update 02-jun-2020：the recommended phase ii doses is 25mg d1-14\] step 2 is a single-arm phase 2 study with fixed does of r2-mtx regimen in newly-diagnosed pcnsl patients. the response will be evaluated every 2 cycles. patients who achieved complete remission (cr) or partial remission (pr) will receive further treatment, and there are 6 cycles of r2-mtx regimen for the induction. the patients with stable disease (sd) or progressed disease (pd) will withdraw from the trial and receive salvage regimens. after total 6 induction cycles, the investigators evaluate the efficiency again, the patients with cr or pr will go to lenalidomide maintenance for 2 years or until progression of the disease (pd), unacceptable toxicity, or patient/investigator discretion. and the patients with sd or pd will receive salvage regimen. \[update 02-jun-2020：younger patients(≤60 years) who achieve pr after 6 cycles of induction therapy will be candidates of high-dose chemotherapy and stem cell rescue. lenalidomide maintenance will be administed after the high-dose chemotherapy. older patients(\>60 years) who achieve pr after 6 cycles of induction will go to lenalidomide maintenance directly.\] during following-up, surveillance examination and brain magnetic resonance imaging (mri) scans can be performed every 3 months up to the first 2 years, followed by doctor visit every 6 months up to 5 years or the disease relapses.

Eligibility criteria:
inclusion criteria: * newly-diagnosed primary vitreoretinal lymphoma * ecog≤2 * creatinine clearance rate (ccr) ≥ 50ml/h, according to cockcroft-gault * total bilirubin \< 2 upper limits of normal, alanine aminotransferase（alt） \< 3 upper limits of normal * hiv-ab negative * sign the informed consent * women of childbearing potential must understand that the study medication could have a potential teratogenic risk. they should undergo complete contraception during the study period. * male subjects must agree to use condoms throughout study drug therapy. exclusion criteria: * pre-existing uncontrolled active infection * clinical evidence of grade 3 or 4 heart failure as defined by the new york heart association criteria * systemic lymphoma involved cns * pregnancy or active lactation * co-existing tumors

Keywords: lenalidomide rituximab methorexate primary central nervous system lymphoma maintenance therapy