ZR-MTX for PIOL Phase II Trial
- Conditions
- Primary Intraocular Lymphoma
- Interventions
- Registration Number
- NCT06973811
- Lead Sponsor
- Peking Union Medical College Hospital
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 47
-
• 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.
-
• 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ZRMTX Methotrexate Zanubrutinib/Rituximab/IV MTX \& intravitreal MTX Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 4 cycles, ZR plus iv MTX for 2 cytles and followed by zanubrutinib maintenance for 2 years ( or choose to stop zanubrutinib maintenance if reached CR with negative CSF cfDNA). Meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment. ZRMTX Rituximab (R) Zanubrutinib/Rituximab/IV MTX \& intravitreal MTX Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 4 cycles, ZR plus iv MTX for 2 cytles and followed by zanubrutinib maintenance for 2 years ( or choose to stop zanubrutinib maintenance if reached CR with negative CSF cfDNA). Meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment. ZRMTX Zanubrutinib Zanubrutinib/Rituximab/IV MTX \& intravitreal MTX Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 4 cycles, ZR plus iv MTX for 2 cytles and followed by zanubrutinib maintenance for 2 years ( or choose to stop zanubrutinib maintenance if reached CR with negative CSF cfDNA). Meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment. ZRMTX Methotrexate (MTX) Zanubrutinib/Rituximab/IV MTX \& intravitreal MTX Experimental arm will be treated with rituximab plus zanubrutinib (ZR) regimen for 4 cycles, ZR plus iv MTX for 2 cytles and followed by zanubrutinib maintenance for 2 years ( or choose to stop zanubrutinib maintenance if reached CR with negative CSF cfDNA). Meanwhile, intravitreal methotrexate will be given as protocol during the 1st year of treatment.
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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