Orelabrutinib plus rituximab versus R‑CVP as first-line treatment for marginal zone lymphoma

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).

This test will see if orelabrutinib plus rituximab, followed by orelabrutinib maintenance, works as well or better than standard R‑CVP chemotherapy for adults with untreated marginal zone lymphoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Nanchang University (Academic / other)
• Drugs / interventions: rituximab, orelabrutinib
• Locations: 1 site (Nanchang, Jiangxi)
• Trial ID: NCT06700798 on ClinicalTrials.gov

What this trial studies

This randomized, open‑label Phase II trial enrolls adults with treatment‑naive, CD20‑positive marginal zone lymphoma who require systemic therapy. Participants are assigned to receive either a chemo‑free regimen of orelabrutinib plus rituximab followed by orelabrutinib maintenance, or the conventional R‑CVP chemotherapy regimen. The trial tracks efficacy endpoints such as response rates and progression‑free survival along with safety and adverse events. The aim is to determine whether the chemo‑free approach can achieve comparable or improved disease control with a different toxicity profile.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with confirmed CD20‑positive marginal zone lymphoma, measurable disease, ECOG 0–2, normal major organ function, and no prior systemic treatment for MZL.

Not a fit: Patients who have received prior systemic therapy for MZL, have poor organ function or uncontrolled comorbidities, are pregnant, or have CD20‑negative disease are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the chemo‑free orelabrutinib plus rituximab approach could control lymphoma while reducing exposure to cytotoxic chemotherapy and its side effects.

How similar studies have performed: Orelabrutinib and other second‑generation BTK inhibitors have shown promising activity in relapsed/refractory MZL, but prospective first‑line data for chemo‑free regimens remain limited.

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.

Where this trial is running

Nanchang, Jiangxi

• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Recruiting)

Study contacts

• Principal investigator: Fei Li, professor — The First Affiliated Hospital of Nanchang University
• Study coordinator: Yulan Zhou Doctor, PhD

Conditions Marginal Zone Lymphoma; Orelabrutinib combined with Rituximab versus R-CVP