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Oxygen Study-Orelabrutinib Combined With Obinutuzumab(O2) for First-Line Treatment of Marginal Zone Lymphoma

Oxygen Study-Orelabrutinib Combined With Obinutuzumab(O2) for First-Line Treatment of Marginal Zone Lymphoma

Recruiting
18 years and older
All
Phase 2

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Overview

This is a multi-center, prospective study. The main purpose is to evaluate the efficacy and safety of Orelabrutinib combined with Obinutuzumab for previously untreated MZL.

Description

Marginal zone lymphoma (MZL) is a relatively common type of B-cell non-Hodgkin lymphoma (B-NHL), with an incidence rate second only to diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). It is divided into three subtypes based on different clinical manifestations and pathological characteristics: mucosa-associated lymphoid tissue lymphoma (MALT), also known as extranodal marginal zone lymphoma, nodal marginal zone lymphoma (NMZL), and splenic marginal zone lymphoma (SMZL). Currently, there is no unified and standardized treatment plan for newly diagnosed MZL. Although high-intensity immunochemotherapy regimens have a high remission rate, they also bring higher treatment-related safety risks. Therefore, exploring effective chemotherapy-free regimens for MZL patients is an attempt with scientific value and clinical significance. With the development of new drugs, new drug regimens have become prominent in the treatment of MZL, and there is an increasing amount of research data on BTK inhibitors in the field of MZL. The BTK inhibitor Orelabrutinib has shown good efficacy in MZL and has been approved by the NMPA for the treatment of MZL in patients who have received at least one prior treatment.

This study is a multi-center, prospectivet clinical study for previously untreated MZL.

The patients will be treated with 6 cycles of O2 regimen. Patients with CR/PR after 6 cycles of O2 treatment will be treated with 1 year of single-agent orelabrutinib regimen.

Eligibility

Inclusion Criteria:

  • Aged ≥18 years, gender not limited;
  • Histopathologically confirmed CD20-positive marginal zone lymphoma including MALT, SMZL, NMZL;
  • MZL that has progressed, recurred, or is not suitable for local treatment after previous local treatment (local treatments include surgery, radiotherapy, Helicobacter pylori treatment, and hepatitis C treatment);
  • ECOG 0-2;
  • Indication for treatment as judged by the investigator (symptomatic, with cytopenia, at risk of end-organ damage, bulky disease, persistent progression, or patient's desire for treatment);
  • Major organ function meets the following criteria: a) Complete blood count: Absolute neutrophil count ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow invasion, absolute neutrophil count ≥1.0×10^9/L, platelets ≥50×10^9/L, hemoglobin ≥50g/L; b) Blood biochemistry: Total bilirubin ≤1.5 ULN, AST or ALT ≤2 ULN; serum creatinine ≤1.5 ULN; serum amylase ≤ULN; c) Coagulation function: International normalized ratio (INR) ≤1.5 ULN.
  • Expected survival time ≥3 months;
  • Voluntarily sign a written informed consent form before the trial screening.

Exclusion Criteria:

  • Currently or previously diagnosed with other malignant tumors, unless curative treatment has been performed and there is evidence of no recurrence or metastasis within the last 5 years;
  • Lymphoma involving the central nervous system or transformation to a higher grade;
  • Active bleeding within 2 months prior to screening, or currently taking anticoagulant medications, or the investigator considers there to be a definite bleeding tendency;
  • Major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening;
  • Active infection or uncontrolled HBV (positive for HBsAg and/or HBcAb and positive for HBV DNA titer), HCV Ab positive, HIV/AIDS, or other serious infectious diseases;
  • Any mental or cognitive disorder that may limit the understanding, execution, and compliance with the informed consent form and the study;
  • Pregnant or lactating women and women of childbearing age who are unwilling to take contraceptive measures;
  • Need to continuously take drugs with moderate to severe inhibitory or strong inductive effects on cytochrome P450 CYP3A;
  • Other conditions that the investigator considers unsuitable for participating in this trial.

Study details
    Marginal Zone Lymphoma

NCT06566807

Huai'an First People's Hospital

15 October 2025

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