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Intravitreal MTX and ZR Regimen in Newly Diagnosed PVRL

Phase 2
Conditions
Primary Vitreoretinal Lymphoma
Interventions
Registration Number
NCT04899453
Lead Sponsor
Peking Union Medical College Hospital
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
42
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Zanubrutinib/rituximab & intravitreal MTXMethotrexateExperimental 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.
Zanubrutinib/rituximab & intravitreal MTXZanubrutinibExperimental 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.
Zanubrutinib/rituximab & intravitreal MTXRituximabExperimental 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.
Primary Outcome Measures
NameTimeMethod
2 years progression-free survivalfrom the date of treatment to the subject finished his 2 years follow-up phase or the disease relapsed or the death due to lymphoma

2 years progression-free survival was calculated from the date of therapy until death from lymphoma or 2-year follow up without relapsing

Secondary Outcome Measures
NameTimeMethod
overall response rate (ORR)4 weeks after the end of 6 cycles of induction (each cycle is 21 days)

ORR was calculated by the proportion of patients who achieved complete remission and partial remission

Trial Locations

Locations (1)

Peking Union Medical College Hospital

🇨🇳

Beijing, Beijing, China

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