Clinical trial NCT04899453: Intravitreal MTX and ZR Regimen in Newly Diagnosed PVRL
Official title: Combined Intravitreal Methotrexate and ZR (Zanubrutinib& Rituximab) Regimen Followed by Zanubrutinib Maintenance in Newly-diagnosed Primary Vitreoretinal Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Primary Vitreoretinal Lymphoma
Keywords: intravitreal methotrexate injection
rituximab
Primary vitreoretinal lymphoma
zanubrutinib
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2021-05-24
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 ZR regimen (rituximab \& Zanubrutinib) combined with intravitreal methotrexate and followed by Zanubrutinib 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 ZR regimen (Rituximab 375mg/m2 IV d1, Zanubrutinib 160mg Bid, 21 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 ZR 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 Zanubrutinib 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 a 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 the 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 or HBV or HCV

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 21 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
References: