Primary Intraocular Lymphoma
Conditions
Keywords
primary intraocular lymphoma
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.
Interventions
DRUGMethotrexate
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
DRUGRituximab (R)
Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
DRUGZanubrutinib
160mg Bid, oral. 21-day cycle for 6 cycles in the induction phase and for 2 years in the maintenance phase
DRUGMethotrexate (MTX)
Methotrexate 3.5g/m2 intravenous infusion d1, every 21 days for cycle 5 and 6 only.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
China
Contacts
Primary ContactWei Zhang, M.M.
Outcome results
None listed