MZL-IPI–guided targeted therapy for untreated marginal zone lymphoma

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

This trial will try different targeted drug combinations based on MZL-IPI risk to treat adults newly diagnosed with marginal zone lymphoma who need systemic therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 145 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 3 sites (Shanghai, China and 2 other locations)
• Trial ID: NCT06793189 on ClinicalTrials.gov

What this trial studies

This Phase 2 study uses the MZL-IPI score to assign newly diagnosed or relapsed marginal zone lymphoma patients who need systemic treatment to different targeted therapy regimens. Treatment arms include combinations and single agents such as obinutuzumab, the BTK inhibitor orelabrutinib, and lenalidomide. The trial will monitor response rates, duration of response, and safety to determine whether risk-adapted regimens improve outcomes. Enrollment occurs at several tertiary hospitals in China and treatment is delivered according to protocol-specified schedules.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed CD20-positive marginal zone lymphoma who require systemic therapy per standard criteria are ideal candidates.

Not a fit: Patients who do not require systemic treatment, have CD20-negative disease, or cannot travel to the participating centers are unlikely to benefit from joining.

Why it matters

Potential benefit: If successful, this approach could personalize therapy and improve remission rates while reducing unnecessary toxicity for patients with MZL.

How similar studies have performed: BTK inhibitors and anti-CD20 antibodies have shown activity in MZL in prior studies, and combinations including lenalidomide have shown promise, though a formal MZL-IPI–guided approach is less well established.

Eligibility criteria

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.

Where this trial is running

Shanghai, China and 2 other locations

• Shanghai Ruijin Hospital — Shanghai, China, China (RECRUITING)
• Affiliated First Hospital of China Medical University — Shenyang, Liaoning, China (RECRUITING)
• Peking University Third Hospital — Beijing, China (RECRUITING)

Study contacts

• Study coordinator: Weili Zhao

Conditions: Marginal Zone Lymphoma