Clinical trial NCT04120350: R2-MTX With Lenalidomide Maintenance in Newly-diagnosed PCNSL：a Multicenter Phase Ib/II Stuty
Official title: R2-MTX Regimen Combined With Lenalidomide Maintenance as Frontline Therapy for Primary Central Nervous System Lymphoma: a Multicenter Prospective Single Arm Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Primary Central Nervous System Lymphoma
Keywords: lenalidomide
rituximab
methorexate
Primary Central Nervous System Lymphoma
maintenance therapy
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Beijing Tiantan Hospital
name: Xuanwu Hospital, Beijing
name: Peking University Third Hospital
name: Beijing Hospital
name: Peking University First Hospital
name: Chinese PLA General Hospital
First posted: 2019-10-09
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Primary outcomes:
measure: 2 years progression-free survival
timeFrame: 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
Secondary outcomes:
measure: 2 years overall survival
timeFrame: From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years
measure: dose-limiting toxicity（DLT）
timeFrame: from the start of the first dose of lenalidomide to the finish of first cycle of induction(21 days for each cycle).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Daobin Zhou
state: Dongcheng District
Study officials:
References: