Clinical trial NCT03746223: Intravitreal Methotrexate and R2(Rituximab & Lenalidomide) Regimen in Newly-diagnosed Primary Vitreoretinal Lymphoma
Official title: Combined Intravitreal Methotrexate and R2 Regimen Followed by Lenalidomide Maintenance in Newly-diagnosed Primary Vitreoretinal Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Primary Intraocular Lymphoma
Keywords: intravitreal methotrexate injection
rituximab
lenalidomide
Primary vitreoretinal lymphoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2018-11-19
Enrollment: 42
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 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 2 years progression-free survival
timeFrame: 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 outcomes:
measure: overall response rate(ORR)
timeFrame: 4 weeks after the end of 6 cycles of induction (each cycle is 28 days).
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union medical college hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang Y, Zhang X, Zou D, Yin J, Zhang L, Wang X, Jia C, Wang W, Zhao D, Zhou D, Zhang W, Zhang M. Lenalidomide and Rituximab Regimen Combined With Intravitreal Methotrexate Followed by Lenalidomide Maintenance for Primary Vitreoretinal Lymphoma: A Prospective Phase II Study. Front Oncol. 2021 Jun 24;11:701507. doi: 10.3389/fonc.2021.701507. eCollection 2021.