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

Official title

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).

Overview

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

Detailed description

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.

Interventions

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

Primary outcome measures

• CRR [Time frame: up to two years]

Secondary outcome measures (3)

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

Eligibility criteria

Inclusion criteria

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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Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Nanchang University — Nanchang

Identifiers

NCT: NCT06700798 · ORRIS

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗