NCT06973811

ZR-MTX for PIOL Phase II Trial

A Prospective, Phase II Clinical Trial Using the Combination of Zanubrutinib, Rituximab and High-dose Intravenous Methotrexate With Intravitreal Methotrexate Injection Therapy for the Treatment of Primary Intraocular Lymphoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 47 (estimated)
• Sponsor: Peking Union Medical College Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective single-arm phase II study, with the purpose of evaluating the efficiency of ZR-MTX regimen (Rituximab, Zanubrutinib and methotrexate) combined with intravitreal methotrexate, then followed by minimal residual disease directed Zanubrutinib maintenance in newly-diagnosed primary intraocular lymphoma. The primary endpoint of this study is progression-free survival (PFS).

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. The response will be evaluated after 2 cycles of ZR regimen. Patients who achieved complete remission (CR) or partial remission (PR) or stable disease (SD) will receive 2 more cycles of ZR regimen. The patients with progressed disease (PD) will withdraw from the trial and receive salvage regimens. Then 2 more cycle of ZR regimen will be administrated. Patients will be evaluated again, those achieved CR or PR or SD will continue to receive 2 cycles of ZR-MTX regimen (Rituximab 375mg/m2 IV d1, Methotrexate 3.5g/m2 IV d1, Zanubrutinib 160mg Bid, 21 days per cycle), while those PD will drop out. In the meantime, intravitreal methotrexate will be given at a dose of 400ug for 16 doses. After total 6 induction cycles, the investigators evaluate the efficiency again, the patients with CR and MRD negativity (by CSF IL-10 and cfDNA) will stop treatment. Those with MRD positive CR or PR or SD 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 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's visit every 6 months for up to 5 years or disease relapses.

Conditions

• Primary Intraocular Lymphoma

Interventions

Type	Name	Description
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 (R)	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
DRUG	Methotrexate (MTX)	Methotrexate 3.5g/m2 intravenous infusion d1, every 21 days for cycle 5 and 6 only.

Timeline

• Start date: 2025-05-10
• Primary completion: 2027-10-30
• Completion: 2029-10-30
• First posted: 2025-05-15
• Last updated: 2025-05-20

Locations

1 site across 1 country: China