Intravitreal MTX and ZR Regimen in Newly Diagnosed PVRL

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Enrolling; Phase 2

Conditions: Primary Vitreoretinal Lymphoma

Treatments: Drug: Methotrexate; Drug: Zanubrutinib; Drug: Rituximab

Study type: Interventional

Funder types: Other

Identifiers

NCT04899453

PUMCH-NHL-007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 42 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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42 participants in 1 patient group

Zanubrutinib/rituximab & intravitreal MTX

Experimental group

Description:

Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 6 cycles and followed by zanubrutinib maintenance for 2 years, meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment.

Treatment:

Drug: Rituximab

Drug: Zanubrutinib

Drug: Methotrexate