MZL-IPI Risk-adapted Targeted Therapy in Untreated MZL

A Prospective Study to Evaluate the Efficacy and Safety of MZL-IPI Risk-adapted Targeted Therapy in Patients With Untreated Marginal Zone B-cell Lymphoma

Marginal zone lymphoma (MZL) is a common type of indolent lymphoma that originates from the marginal zone of lymphoid follicles. This study aims to evaluate targeted therapy based on the prognostic risk stratification of MZL-IPI in newly diagnosed MZL cases requiring systemic treatment, and provides a basis for precision treatment of MZL.

Study Overview

• Status: Recruiting
• Conditions: Marginal Zone Lymphoma(MZL)
• Intervention / Treatment: Drug: Obinutuzumab and Orelabrutinib; Drug: Orelabrutinib; Drug: Obinutuzumab, Orelabrutinib and Lenalidomide

• Study Type: Interventional
• Enrollment (Estimated): 145
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: +862164370045; Email: zwl_trial@163.com
• Study Contact Backup: Name: Pengpeng Xu; Phone Number: +862164370045; Email: pengpeng_xu@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Hongmei Jing; Email: hongmeijing@bjmu.cn
  • China
    • Shanghai, China, China, 200025
      • Recruiting
      • Shanghai Ruijin Hospital
      • Contact: Yujia Huo; Phone Number: 13302066917; Email: zhao.weili@yahoo.com
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Affiliated First Hospital of China Medical University
      • Contact: Xiaojing Yan; Email: yanxiaojing_pp@hotmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Histopathologically confirmed CD20-positive marginal zone lymphoma (according to the 2016 WHO classification).

  2. Age ≥ 18 years old, regardless of gender. 3. MZL patients requiring systemic treatment, including but not limited to:

  1. Helicobacter pylori (HP)-positive or HP - negative gastric mucosa extranodal marginal zone lymphoma (MALT) patients with progression/relapse after local treatment (including surgery, radiotherapy, and anti - Helicobacter pylori treatment).
  2. Non - gastric MALT patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.
  3. Splenic marginal zone lymphoma (SMZL) patients with progression/relapse after local treatment (including splenectomy, antiviral treatment for HCV - positive patients, etc.), or untreated patients meeting the criteria of progressive or painful splenomegaly, symptomatic or progressive cytopenia such as HB < 100g/L, PLT < 80×10⁹/L, absolute neutrophil count (ANC) < 1.0×10⁹/L.
  4. Nodal marginal zone lymphoma (NMZL) patients with Ann Arbor stage I - II who have progression/relapse after local treatment (including surgery, radiotherapy, etc.), or untreated patients with Ann Arbor stage III - IV who meet the GELF criteria recommended by the NCCN guidelines.

  4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2. 5. Life expectancy of at least 3 months. 6. The patient has adequate bone marrow (except those caused by MZL), liver and kidney functions.

  7. Able to comply with the research procedures and cooperate in the implementation of the entire research process; 8. Written informed consent; 9. Women with fertility agree to take appropriate measures to avoid pregnancy during the treatment period until at least one year after the end of treatment; Men agree to maintain abstinence or use barrier contraception.

Exclusion Criteria:

• 1. Histologically transformed into high-grade lymphoma. 2. Known central nervous system involvement of MZL. 3. Previous systemic treatment including immunotherapy, chemotherapy or targeted drugs.

  4. Previous autologous stem-cell transplantation or allogeneic tissue/solid organ transplantation.

  5. History of other invasive cancers within the past 3 years that have not received curative treatment or are still receiving anti-cancer treatment (including hormonal therapy for breast or prostate cancer).

  6. Complicated with uncontrolled cardiovascular and cerebrovascular diseases (such as New York Heart Association-defined grade 3 or 4 heart failure, arrhythmia, myocardial infarction, stroke, or intracranial hemorrhage), coagulation - disorder diseases, connective tissue diseases, severe infectious diseases (including active pulmonary tuberculosis), etc.

  7. Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C virus infection (positive result shown by polymerase chain reaction [PCR]). Serological antibody - positive is allowed if HBV DNA < 10³ IU/ml; HCV RNA test must be negative.

  8. Vaccinated with live attenuated vaccines within 4 weeks before starting investigational treatment. During the study, patients are prohibited from receiving live attenuated vaccine inoculations, including influenza vaccines.

  9. Requiring continuous treatment with potent and moderate-effect CYP3A inhibitors or CYP3A inducers.

  10. Unable to swallow capsules or having diseases that significantly affect gastrointestinal function, such as malabsorption syndrome, bariatric surgery, inflammatory bowel disease, or partial or complete intestinal obstruction.

  11. Psychiatric patients or other patients known or suspected to be unable to fully comply with the study protocol.

  12. Pregnant or lactating women. 13. Other concurrent and uncontrolled medical conditions that, in the investigator's opinion, will affect the patient's participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obinutuzumab and Orelabrutinib (O2) regimen; Low-risk patients (MZL-IPI 0-2 points)	Drug: Obinutuzumab and Orelabrutinib; Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days) and Orelabrutinib (150 mg once daily).; Drug: Orelabrutinib; Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).
Experimental: Obinutuzumab, Orelabrutinib and Lenalidomide (O2R) regimen; High-risk patients (MZL-IPI 3-5 points)	Drug: Orelabrutinib; Maintenance: Orelabrutinib monotherapy (150 mg once daily up to 24 months).; Drug: Obinutuzumab, Orelabrutinib and Lenalidomide; Induction: Obinutuzumab (1000 mg on days 1, 8, and 15 of cycle 1; 1000 mg on day 1 of cycles 2-6, cycle length=21 days), Orelabrutinib (150 mg once daily), and Lenalidomide (25 mg on days 2-11 of cycles 1-6, cycle length=21 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year progression-free survival	Progression-free survival is defined as the time from registration to the first occurrence of disease progression or relapse, using 2014 Lugano criteria, or death from any cause, whichever occurred first; as assessed by the investigator.	Baseline up to data cut-off (up to 24 months).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate after 6 cycles, at 12 months and 24 months	The proportion of patients with complete response after 6 cycles, 12 months and 24 months from treatment start, according to the 2014 Lugano Response Criteria.	At the end of cycle 6, at 12 months and 24 months after treatment start.
Overall Response Rate after 6 cycles, at 12 months and 24 months	The proportion of patients with complete and partial response after 6 cycles, 12 months and 24 months from treatment start, according to the 2014 Lugano Response Criteria.	At the end of cycle 6, at 12 months and 24 months after treatment start.
Treatment-Related Adverse Events rate as assessed by CTCAE version 5.0		From enrollment to study completion (up to approximately 24 months).
Duration of Response (DOR)	Duration of response is defined as the period from the first response (at least PR) to treatment until evidence of disease progression, relapse or death of any cause.	From enrollment to study completion (up to approximately 24 months).
Histological transformation rate	Histological transformation rate is defined as the proportion of patients with histological transformation.	From enrollment to study completion (up to approximately 24 months).
2-year overall survival	Overall survival is defined as the time from registration to death from any cause.	Baseline up to data cut-off (up to 24 months).

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: January 20, 2025
• First Posted (Actual): January 27, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

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; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; obinutuzumab; orelabrutinib
• Other Study ID Numbers: MAGIC (Alias Study Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No