ZR-MTX for PIOL Phase II Trial

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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
• Препарат Rituximab (R)
  Rituximab 375mg/m2 intravenous infusion d1, every 21 days for 1 cycle. 6 cycles will be prescribed as protocol
• Препарат Zanubrutinib
  160mg Bid, oral. 21-day cycle for 6 cycles in the induction phase and for 2 years in the maintenance phase
• Препарат Methotrexate (MTX)
  Methotrexate 3.5g/m2 intravenous infusion d1, every 21 days for cycle 5 and 6 only.

Первичные конечные точки

• 2 years progression-free survival [Срок оценки: 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]

Вторичные конечные точки (1)

• overall response rate (ORR) [Срок оценки: 4 weeks after the end of 6 cycles of induction (each cycle is 21 days).]

Критерии участия

Критерии включения

• • 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.

Критерии исключения

• • 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Peking Union Medical College Hospital — Пекин

Идентификаторы

NCT: NCT06973811 · K6396

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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