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

Fei Li

Status and phase: Enrolling; Phase 2

Conditions: Marginal Zone Lymphoma(MZL)

Treatments: Drug: rituximab; Drug: Prednisone tablet; Drug: Orelabrutinib; Drug: Cyclophosphamide; Drug: Vincristine

Study type: Interventional

Funder types: Other

Identifiers

NCT06700798

ORRIS

Details and patient eligibility

About

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

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Exclusion criteria

1. Patients with central nervous system involvement;
2. History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
3. 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%;
4. 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;
5. 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;
6. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
7. Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;
8. Factors that significantly affect the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
9. Active infections requiring antimicrobial treatment (e.g., requiring antibacterial, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal treatment);
10. 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);
11. History of substance abuse and inability to quit or mental disorders;
12. Participation in other anticancer drug clinical trials within 4 weeks prior to enrollment;
13. 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;
14. Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures;
15. Other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 2 patient groups

OR-R

Experimental group

Description:

Orelabrutinib 150mg, oral, once daily, Days 1-28, with a cycle of 4 weeks; Cycles 1-24； Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 4 weeks; Cycles 1-6

Treatment:

Drug: Orelabrutinib

Drug: rituximab

R-CVP

Active Comparator group

Description:

Rituximab: 375mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks; Cycles 1-8； Cyclophosphamide: 750mg/m\^2, intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Vincristine: 1.4mg/m\^2 (maximum 2mg), intravenous, Day 1, with a cycle of 3 weeks;Cycles 1-8； Prednisone: 60mg/m\^2, oral, Days 1-5, with a cycle of 3 weeks，Cycles 1-8 Subsequently, maintenance with rituximab monotherapy until two years from the start of treatment or until toxicity intolerable.

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Prednisone tablet

Drug: rituximab