Orelabrutinib alone or with a CD20 antibody for people newly diagnosed with marginal zone lymphoma

Application of Orelabrutinib With or Without CD20 Monoclonal Antibody in Previously Untreated Marginal Zone Lymphoma:A Phase II, Prospective, Multicenter, Single-Arm Clinical Study

This trial tests if orelabrutinib by itself or together with a CD20 antibody can treat adults who have just been diagnosed with marginal zone lymphoma.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 88 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Beijing Tongren Hospital (Academic / other)
• Drugs / interventions: Rituximab, Obinutuzumab, orelabrutinib, chemotherapy
• Locations: 3 sites (Beijing and 2 other locations)
• Trial ID: NCT07355699 on ClinicalTrials.gov

What this trial studies

This single-arm, phase 4 study enrolls treatment-naïve adults with pathologically confirmed marginal zone lymphoma and assigns therapy based on stage and clinical features. Patients with Stage I disease receive orelabrutinib monotherapy (150 mg once daily, days 1–21 of each cycle for six cycles), while those with Stage II–IV disease receive orelabrutinib combined with a CD20 monoclonal antibody per protocol. Tumor response is measured by overall and complete response rates using imaging and laboratory tests, and safety is recorded through detailed adverse event monitoring. Long-term follow-up will track progression-free and overall survival to determine whether a chemotherapy-free regimen provides durable benefit.

Who should consider this trial

Good fit: Adults (≥18 years) with pathologically confirmed, treatment-naïve marginal zone lymphoma who have measurable disease and meet treatment indications or are unsuitable for or refuse local radiotherapy are ideal candidates.

Not a fit: Patients who have received prior systemic lymphoma therapy, who lack evaluable lesions, or who have contraindications to BTK inhibitors or CD20 antibodies are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could provide an effective, lower-toxicity, chemotherapy-free first-line option for newly diagnosed MZL patients.

How similar studies have performed: Other BTK inhibitors such as ibrutinib have shown efficacy in MZL and combining BTK inhibitors with CD20 antibodies has biological rationale and some supportive data, but frontline orelabrutinib combination data remain limited.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years;
* Pathologically confirmed marginal zone lymphoma;
* Presence of evaluable lesions;
* Meets indications for treatment: Fulfills the GELF criteria OR has disease-related clinical symptoms/organ function impairment;
* Patients who are unsuitable for local radiotherapy, refuse local radiotherapy, or have disease progression after local therapy. Cases considered unsuitable for local radiotherapy include the following:

Gastric MALT MZL, Ann Arbor stage I, that is H. pylori-negative, or H. pylori-positive gastric MALT MZL (Ann Arbor stage I) with poor response to H. pylori eradication therapy;

Non-gastric MALT and nodal MZL in Ann Arbor non-contiguous stage II or stages III-IV;

SMZL;

Gastric MALT classified as Lugano II2, IIE, or IV stage;

Patient intolerance to radiotherapy;

Other MZL patients deemed unsuitable for local radiotherapy by the investigator.

* ECOG score of 0-3;
* Expected survival time ≥ 3 months;
* Ability to provide signed informed consent.

Exclusion Criteria:

* Currently diagnosed with another malignant tumor;
* Central nervous system involvement by lymphoma or transformation to a higher grade;
* Allergy to any of the investigational drugs;
* Active infection or uncontrolled HBV infection, HIV/AIDS, or other serious infectious diseases;
* Pregnancy, lactating women, or subjects of childbearing potential unwilling to use contraception;
* Other situations deemed by the investigator as unsuitable for participation in this trial.

Where this trial is running

Beijing and 2 other locations

• Beijing Tongren Hospital — Beijing, China (Recruiting)
• Peking Union Medical College Hospital — Beijing, China (Not_yet_recruiting)
• The First Affiliated Hospital of China Medical University — Beijing, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Liang Wang, MD — Beijing Tongren Hospital
• Study coordinator: Liang Wang, MD

Conditions Marginal Zone Lymphoma; Orelabrutinib; CD20 Monoclonal Antibody