Intravitreal MTX and ZR Regimen in Newly Diagnosed PVRL

Sponsor

Peking Union Medical College Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04899453

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Vitreoretinal Lymphoma	Drug: Methotrexate Drug: Rituximab Drug: Zanubrutinib	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Combined Intravitreal Methotrexate and ZR (Zanubrutinib& Rituximab) Regimen Followed by Zanubrutinib Maintenance in Newly-diagnosed Primary Vitreoretinal Lymphoma

Actual Study Start Date :

Aug 1, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Zanubrutinib/rituximab & intravitreal MTX 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.	Drug: Methotrexate 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 Drug: Rituximab Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol Drug: Zanubrutinib 160mg Bid, oral. 21-day cycle for 6 cycles in the induction phase and for 2 years in the maintenance phase

Arm

Intervention/Treatment

Experimental: Zanubrutinib/rituximab & intravitreal MTX

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.

Drug: Methotrexate

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

Drug: Rituximab

Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol

Drug: Zanubrutinib

160mg Bid, oral. 21-day cycle for 6 cycles in the induction phase and for 2 years in the maintenance phase

Outcome Measures

Primary Outcome Measures

2 years progression-free survival [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]
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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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