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

NCT ID: NCT06700798

Last Updated: 2025-06-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2027-12-04

Brief Summary

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.

Conditions

Marginal Zone Lymphoma(MZL)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

OR-R

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

Group Type: EXPERIMENTAL

Orelabrutinib

Intervention Type: DRUG

150mg po

rituximab

Intervention Type: DRUG

375mg/m\^2, intravenous

R-CVP

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.

Group Type: ACTIVE_COMPARATOR

rituximab

Intervention Type: DRUG

375mg/m\^2, intravenous

Cyclophosphamide

Intervention Type: DRUG

750mg/m\^2

Vincristine

Intervention Type: DRUG

1.4mg/m\^2

Prednisone tablet

Intervention Type: DRUG

60mg/m\^2

Interventions

Orelabrutinib

150mg po

Intervention Type: DRUG

rituximab

375mg/m\^2, intravenous

Intervention Type: DRUG

Cyclophosphamide

750mg/m\^2

Intervention Type: DRUG

Vincristine

1.4mg/m\^2

Intervention Type: DRUG

Prednisone tablet

60mg/m\^2

Intervention Type: DRUG

Other Intervention Names

ICP-022

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fei Li

OTHER

Sponsor Role: lead

Responsible Party

Fei Li

Chief physician

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Fei Li, professor

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital of Nanchang University

Locations

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yulan Zhou Doctor, PhD

Role: CONTACT

wenxin_yl@163.com

86-0791-88692743

Facility Contacts

Yulan Zhou doctor, PhD

Role: primary

wenxin_yl@163.com

86-0791-88692748

Other Identifiers

ORRIS

Identifier Type: -

Identifier Source: org_study_id