R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.
试验速览
- 阶段
- 1 期
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- 2 years progression-free survival
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly-diagnosed primary vitreoretinal lymphoma
- •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.
排除标准
- •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
研究组 & 干预措施
R2-MTX-LEN
Phase Ib：Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg， 20mg， 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years.
Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years.
干预措施: Methotrexate (Drug)
R2-MTX-LEN
Phase Ib：Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg， 20mg， 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years.
Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years.
干预措施: Rituximab (Drug)
R2-MTX-LEN
Phase Ib：Experimental arm will be treated with R2-MTX regimen for 6 cycles as initiate induction, the dose of lenalidomide was escalated from 15mg， 20mg， 25mg to test DLT by 3+3 design, meanwhile the dose of rituximab and methotrexate is fixed. If the patients achieved CR or PR by MRI and CSF evaluation, they processed to lenalidomide maintenance for 2 years.
Phase II: the patients will be treated by fixed dose of R2-MTX regimen (established lenalidomide dose from phase Ib study) for 6 cycles. the efficiency evaluation will be performed every 2 cycles, the patients who achieved CR or PR will finish the total 6 cycles of induction therapy, then begin the stage of lenalidomide maintenance for 2 years. Follow-ups should be taken for 5 years.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
2 years progression-free survival
时间窗: From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing
次要结局
- dose-limiting toxicity（DLT）(from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).)
- 2 years overall survival(From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years)