Application of Orelabrutinib With or Without CD20 Monoclonal Antibody in Previously Untreated Marginal Zone Lymphoma

NCT07355699 | Recruiting Phase 4 DMC

• 1 other identifier: TREC2025-KY209
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 3

Brief Summary

This study focuses on treatment-naïve marginal zone lymphoma (MZL) patients and aims to investigate the efficacy and safety of orelabrutinib combined with or without CD20 monoclonal antibody. This is a single-arm study without a control group. All subjects will receive orelabrutinib treatment but will be stratified based on disease stage and clinical characteristics into the following two groups:

1. 1.Stage I MZL Patient Group (Monotherapy Group) Treatment regimen: Orelabrutinib monotherapy. Dosage and administration: Orelabrutinib 150mg, once daily (qd), taken continuously for 21 days per treatment cycle (d1-d21), for a total of 6 cycles (C1-C6).
2. 2.Stage II-IV MZL Patient Group (Combination Therapy Group) Treatment regimen: Orelabrutinib combined with a CD20 monoclonal antibody. Dosage and administration: Orelabrutinib 150mg, once daily (qd), taken continuously for 21 days per treatment cycle (d1-d21), for a total of 6 cycles (C1-C6). CD20 monoclonal antibody (either Rituximab 375mg/m², intravenous infusion, Day 1 of each cycle, C1-C6; or Obinutuzumab 1000mg, intravenous infusion, on Days 1, 8, and 15 of Cycle 1 \[C1\], and on Day 1 of Cycles 2-6 \[C2-C6\]).

Conditions

Marginal Zone Lymphoma(MZL)

Keywords

Marginal Zone Lymphoma; Orelabrutinib; CD20 Monoclonal Antibody

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Best Overall Response Rate (ORR): Efficacy is assessed every two treatment cycles. The best ORR achieved within the 6 treatment cycles serves as the primary endpoint.

  From enrollment to the end of treatment at 21 weeks

Secondary Outcomes (4)

• Complete Response Rate

  From enrollment to the end of treatment at 21 weeks

• 2-Year Progression-Free Survival Rate

  From enrollment to 2 years

• 2-Year Overall Survival Rate

  From enrollment to 2 years

• AE

  Through study completion, an average of 2.5 years

Study Arms (1)

Orelabrutinib-based treatments

EXPERIMENTAL

This is a single-arm study without a control group. All subjects will receive orelabrutinib treatment but will be stratified based on disease stage and clinical characteristics into the following two groups: 1. Stage I MZL Patient Group (Monotherapy Group) Treatment regimen: Orelabrutinib monotherapy. Dosage and administration: Orelabrutinib 150mg, once daily (qd), taken continuously for 21 days per treatment cycle (d1-d21), for a total of 6 cycles (C1-C6). 2. Stage II-IV MZL Patient Group (Combination Therapy Group) Treatment regimen: Orelabrutinib combined with a CD20 monoclonal antibody. Dosage and administration: Orelabrutinib 150mg, once daily (qd), taken continuously for 21 days per treatment cycle (d1-d21), for a total of 6 cycles (C1-C6). CD20 monoclonal antibody (either Rituximab 375mg/m², intravenous infusion, Day 1 of each cycle, C1-C6; or Obinutuzumab 1000mg, intravenous infusion, on Days 1, 8, and 15 of Cycle 1 \[C1\], and on Day 1 of Cycles 2-6 \[C2-C6\].

Drug: Orelabrutinib

Interventions

Orelabrutinib DRUG

1. Stage I MZL Patients: Treatment with Orelabrutinib monotherapy. Induction Phase: During Cycles 1-6 (C1-C6), Orelabrutinib 150mg is administered orally once daily (qd) on Days 1-21 (d1-d21) of each cycle. 2. Stage II-IV MZL Patients: Treatment with the Orelabrutinib plus CD20 monoclonal antibody regimen, divided into an induction phase and a maintenance phase. Induction Phase: During Cycles 1-6 (C1-C6), Orelabrutinib 150mg is administered orally once daily (150mg qd d1-d21/C1-C6). Concurrently, a CD20 monoclonal antibody is used: either Rituximab 375mg/m² intravenously (iv) on Day 1 of each cycle (d1/C1-C6); or Obinutuzumab, administered as 1000mg intravenously on Days 1, 8, and 15 of Cycle 1 (1000mg iv d1,d8,d15/C1), followed by 1000mg intravenously on Day 1 of Cycles 2-6 (1000mg iv d1/C2-C6). Maintenance Phase: If maintenance therapy is administered, during Cycles 7-30 (C7-C30), Orelabrutinib 150mg is administered orally once daily (qd) on Days 1-28 (d1-d28) of each cycle.

Also known as: Rituximab, Obinutuzumab

Orelabrutinib-based treatments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Tongren Hospital: lead

Study Sites (3)

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

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

orelabrutinib; Rituximab; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Liang Wang, MD

  Beijing Tongren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Liang Wang, MD

CONTACT

+86 15013009093; wangliangtrhos@126.com

Wei Zhang, MD

CONTACT

+86 13681473557; vv1223@vip.sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician of Hematology Department

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: January 21, 2026
• Study Start: November 25, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Time Frame: after the publishment of this study
• Access Criteria: upon request to the PI after the publishment of this study

Locations

CN (3)