Intravitreal Methotrexate and R2(Rituximab & Lenalidomide) Regimen in Newly-diagnosed Primary Vitreoretinal Lymphoma

Study Overview
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Brief Summary
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This is a prospective single arm phase II study, and the purpose of this study is to evaluate the efficiency of R2 regimen (rituximab & lenalidomide) combined with intravitreal methotrexate and followed by lenalidomide maintenance in newly-diagnosed primary intraocular lymphoma. Progression free survival (PFS) of the cohort is the primary endpoint.

Detailed Description
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All the patients will be treated with R2 regimen （Rituximab 375mg/m2 IV d1, lenalidomide 25mg d1-21, 28 days per cycle) as induction regimen, meanwhile intravitreal methotrexate was given at a dose of 400ug for 16 doses. The response will be evaluated every 3 cycles. After 3 Cycles, patients who achieved complete remission (CR) or partial remission (PR) will receive 3 more cycles of R2 regimen. 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. During following-up, surveillance ophthalmologic 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.

Official Title
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Combined Intravitreal Methotrexate and R2 Regimen Followed by Lenalidomide Maintenance in Newly-diagnosed Primary Vitreoretinal Lymphoma

Conditions
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Primary Intraocular Lymphoma

Intervention / Treatment
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* Drug: Methotrexate
* Drug: Rituximab
* Drug: Lenalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly-diagnosed primary vitreoretinal lymphoma ECOG≤2 creatinine clearance rate (CCR) ≥ 60ml/h, according to Cockcroft-Gault Total bilirubin < 2 upper limits of normal, alanine aminotransferase（ALT） < 3 upper limits of normal 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: primary central nervous system lymphoma involved eyes and brain systemic B cell lymphoma involved eyes Pre-existing uncontrolled active infection Clinical evidence of grade 3 or 4 heart failure as defined by the New York Heart Association criteria Pregnancy or active lactation Co-existing tumors HIV（human immunodeficiency virus） or HBV（hepatitis B virus） or HCV（hepatitis C virus） infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R2-R/IV-MTX（methotrexate）<br>experimental arm will be treated rituximab plus lenalidomide (R2) regimen for 6 cycles and followed by lenalidomide maintenance for 2 years, meanwhile intravitreal methotrexate will be given as protocol | Drug: Methotrexate<br>* 400ug intravitreal injection every week for 4 doses in the induction phase, every 2 weeks for 2 doses as consolidation, then every month for 10 doses as maintenance<br>Drug: Rituximab<br>* Rituximab：375mg/m2 intravenous infusion d1, every 28 days for 1 cycle. 6 cycles will be prescribed as protocol<br>Drug: Lenalidomide<br>* 25mg Qd, oral , d1-21 in 28-day cycle in the induction phase and maintenance phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2 years progression-free survival | 2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow-up without relapsing | from the date of treatment to the subject finished his 2 years follow-up phase or the disease relapsed or the death due to lymphoma | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate(ORR) | ORR was calculated by the proportion of patients who achieved complete remission and partial remission. | 4 weeks after the end of 6 cycles of induction (each cycle is 28 days). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intravitreal methotrexate injection, rituximab, lenalidomide, Primary vitreoretinal lymphoma