Orelabrutinib Combined With Rituximab Versus R-CVP in the Untreated MZL： A Randomized, Open Phase II Trial

Официальное название

A Randomized, Open-Label Phase II Clinical Study of Orelabrutinib Combined With Rituximab Versus R-CVP in the Treatment of Newly Diagnosed Marginal Zone Lymphoma (MZL).

Обзор

This study is a randomized, open-label, multicenter, prospective clinical trial aimed at evaluating the efficacy and safety of orelabrutinib combined with rituximab for the previously untreat MZL

Подробное описание

For patients with advanced-stage MZL who require treatment, immunochemotherapy is the standard therapy, including regimens such as BR, R-CHOP, R-CVP, etc. The second-generation BTK inhibitor, orelabrutinib, has shown promising efficacy in relapsed/refractory MZL, suggesting that a chemofree regimen combining orelabrutinib with rituximab could also achieve good clinical outcomes in first-line treatment of MZL. However, there is still a lack of prospective studies to confirm this. This study plans to compare the efficacy and safety of orelabrutinib combined with rituximab followed by maintenance therapy with orelabrutinib to the R-CVP regimen.

Вмешательства

• Препарат Orelabrutinib
  150mg po
• Препарат rituximab
  375mg/m\^2, intravenous
• Препарат Cyclophosphamide
  750mg/m\^2
• Препарат Vincristine
  1.4mg/m\^2
• Препарат Prednisone tablet
  60mg/m\^2

Первичные конечные точки

• CRR [Срок оценки: up to two years]

Вторичные конечные точки (3)

• ORR [Срок оценки: up to two years]
• PFS rate at 24month [Срок оценки: Two years after the last patient was enrolled.]
• Safety parameters [Срок оценки: up to 3 years]

Критерии участия

Критерии включения

1.Age ≥18 years； 2.ECOG performance status level 0\~2； 3.Life expectancy of at least 12 weeks; 4.Confirmed CD20-positive marginal zone lymphoma according to the WHO 2008 lymphoma classification criteria, including splenic MZL, nodal MZL, and extranodal MZL subtypes; 5.Measurable lesions detected by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); 6.Indication for treatment according to NCCN guidelines and no prior systemic treatment for MZL; 7.Normal function of major organs; 8.Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization; 9.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.

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Критерии исключения

• Patients with central nervous system involvement;
• History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
• Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval for males ≥450 ms, for females ≥470 ms); Class III to IV heart failure according to NYHA standards, or echocardiography indicating left ventricular ejection fraction (LVEF) <50%;
• Coagulation abnormalities (INR >1.5 or prothrombin time (PT) >ULN+4 seconds or APTT >1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy;
• Arterial/venous thrombotic events within 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
• Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;
• Factors that significantly affect the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
• Active infections requiring antimicrobial treatment (e.g., requiring antibacterial, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal treatment);
• Active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL) or hepatitis C (hepatitis C antibody positive, and HCV RNA above the lower limit of detection of the analytical method);
• History of substance abuse and inability to quit or mental disorders;
• Participation in other anticancer drug clinical trials within 4 weeks prior to enrollment;
• Received treatment with potent CYP3A4 inhibitors within 7 days prior to enrollment, or received treatment with potent CYP3A4 inducers within 12 days prior to study participation;
• Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures;
• Other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Nanchang University — Nanchang

Идентификаторы

NCT: NCT06700798 · ORRIS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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