Clinical trial NCT06973811: ZR-MTX for PIOL Phase II Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Primary Intraocular Lymphoma
Keywords: primary intraocular lymphoma
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2025-05-15
Enrollment: 47
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, 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.

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 infection

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: