Zanubrutinib Plus Rituximab as Front-line Treatment for Mucosa-associated Lymphoid Tissue Lymphoma (MALT)

Zanubrutinib Plus Rituximab as Front-line Treatment for Mucosa-associated Lymphoid Tissue Lymphoma (MALT): a Single-arm, Open-label, Multicenter, Phase II Study（ZAMA）

This is a prospective, single-arm, multicenter, phase II clinical trial to evaluate the efficacy and safety of Zanubrutinib in combination with Rituximab as a first-line treatment for patients with mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.

Study Overview

• Status: Recruiting
• Conditions: Mucosa-associated Lymphoid Tissue Lymphoma (MALT)
• Intervention / Treatment: Drug: Zanubrutinib; Drug: Rituximab

Detailed Description

The purpose of this study is to evaluate the efficacy and safety of Zanubrutinib in combination with Rituximab as a first-line treatment for patients with mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.

Treatrment:

1. Rituximab: 375 mg/m², administered once a week in Cycle 1 (C1) and on Day 1 (D1) of Cycles 2-6 (C2-C6).
2. Zanubrutinib: 160 mg, administered twice daily from Day 1 to Day 28 (D1-D28). Each cycle lasts 28 days. After 6 cycles of treatment, patients who achieve complete remission (CR) will end treatment and enter observation follow-up. Patients with partial remission (PR) or stable disease (SD) will receive 2 additional cycles.

The primary study endpoint is the complete remission rate of Zanubrutinib in combination with Rituximab in the treatment of newly diagnosed mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qingqing Cai, MD. PhD.; Phone Number: 02087342823; Email: caiqq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Recruiting
      • Sun Yat-sen Universitiy Cancer Center, Sun Yat-Sen University
      • Contact: Qingqing Cai; Phone Number: 0086-20-87342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key inclusion Criteria:

1. Mucosa-associated lymphoid tissue (MALT) extranodal marginal zone lymphoma confirmed by histopathology.
2. Newly diagnosed with Ann Arbor stage III-IV or relapsed MALT after local treatment .
3. No prior systemic anti-lymphoma therapy (except for H. pylori eradication therapy in H. pylori-positive gastric MALT patients).
4. No histopathological transformation to high-grade lymphoma.
5. At least one measurable lesion according to the Lugano 2014 criteria.

7. Age ≥ 18 years, with no gender restrictions. 7. An ECOG performance status score of 0-2. 8. An expected survival time of more than 12 months. 9. Adequate bone marrow, cardiac, pulmonary, liver, and kidney function. 10. Willing to participate in the clinical study; fully informed and aware of the study, having signed the informed consent form; willing and able to comply with all study procedures.

Key exclusion Criteria:

1. Patients with a history of stroke, intracranial hemorrhage, or warfarin use within the past 6 months.
2. Patients with central nervous system involvement.
3. Patients who have undergone allogeneic hematopoietic stem cell transplantation in the past.
4. Patients who have previously used BTK inhibitors or received CD20 monoclonal antibody therapy.

5, Patients with active infections, except for tumor-related B-symptom fever. 6. Patients with a concurrent history of other malignancies, except for cured cervical carcinoma in situ or basal cell carcinoma of the skin.

7. Patients receiving potent cytochrome P450 inhibitors. 8. Patients with severe cardiovascular diseases, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or a history of myocardial infarction within the past 12 months.

9. Patients, as judged by the investigator, who have significant organ dysfunction or uncontrollable comorbidities that pose a safety risk, or who have absorption and metabolism issues with Zanubrutinib.

10. Pregnant or breastfeeding women and women of childbearing age unwilling to use contraception.

11. Patients who have received anti-tumor therapy within 4 weeks prior to enrollment.

12. Patients with active chronic hepatitis B or active hepatitis C. 13. Patients who have received systemic corticosteroid treatment or other immunosuppressive therapy within 14 days prior to the start of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Zanubrutinib in combination with Rituximab; Eligible patients will receive: Rituximab: 375 mg/m², administered once a week during Cycle 1 (C1), and on Day 1 (D1) of Cycles 2-6 (C2-C6).; Zanubrutinib: 160 mg, administered twice daily from Day 1 to Day 28 (D1-D28). Each cycle lasts 28 days. After 6 cycles of treatment, patients who achieve complete remission (CR) will end treatment and enter observation follow-up, while patients with partial remission (PR) or stable disease (SD) will receive an additional 2 cycles.

Drug: Zanubrutinib; 160 mg, administered twice daily from Day 1 to Day 28 (D1-D28); Drug: Rituximab; 375 mg/m², administered once a week during Cycle 1 (C1), and on Day 1 (D1) of Cycles 2-6 (C2-C6)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response(CR)	Defined as the proportion of patients who achieve complete remission as the best response	Up to 8 cycles (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The proportion of patients who achieve complete remission (CR) or partial remission (PR) as the best response.	Up to 8 cycles (each cycle is 28 days)
Progression-free survival(PFS)	To investigate the preliminary anti-tumor efficacy	From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Event-free survival(EFS)	To investigate the preliminary anti-tumor efficacy	The proportion of patients without disease progression, treatment discontinuation, or death for any reason since enrollment, assessed up to 24 months
Overall survival(OS)	To investigate the preliminary anti-tumor efficacy	From the date of enrollment until the date of death from ant cause, assessed up to 24 months
Duration of Response(DOR)	To investigate the preliminary anti-tumor efficacy	The time from the patient's first efficacy assessment achieving CR or PR until disease progression, assessed up to 24 months
Time to Response(TTR)	To investigate the preliminary anti-tumor efficacy	The time from the start of patient enrollment in the trial to the first efficacy assessment achieving CR or PR, assessed up tp 24 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: Beijing Tongren Hospital; Shenzhen People's Hospital; Fifth Affiliated Hospital, Sun Yat-Sen University; Gansu Cancer Hospital; Fifth Affiliated Hospital of Guangzhou Medical University; Tongji Medical College of Huazhong University of Science & Technology; Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: October 16, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 13, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, B-Cell, Marginal Zone; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; zanubrutinib
• Other Study ID Numbers: B2024-594-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No