Orelabrutinib plus rituximab versus R‑CVP as first-line treatment for marginal zone lymphoma

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This randomized, open‑label Phase II trial enrolls adults with treatment‑naive, CD20‑positive marginal zone lymphoma who require systemic therapy. Participants are assigned to receive either a chemo‑free regimen of orelabrutinib plus rituximab followed by orelabrutinib maintenance, or the conventional R‑CVP chemotherapy regimen. The trial tracks efficacy endpoints such as response rates and progression‑free survival along with safety and adverse events. The aim is to determine whether the chemo‑free approach can achieve comparable or improved disease control with a different toxicity profile.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1.Age ≥18 years； 2.ECOG performance status level 0\~2； 3.Life expectancy of at least 12 weeks; 4.Confirmed CD20-positive marginal zone lymphoma according to the WHO 2008 lymphoma classification criteria, including splenic MZL, nodal MZL, and extranodal MZL subtypes; 5.Measurable lesions detected by enhanced computed tomography (CT) or magnetic resonance imaging (MRI); 6.Indication for treatment according to NCCN guidelines and no prior systemic treatment for MZL; 7.Normal function of major organs; 8.Women of childbearing age must have taken reliable contraceptive measures or undergone a pregnancy test (serum or urine) within 7 days before enrollment, with a negative result, and must be willing to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication. For men, they must agree to use appropriate contraceptive methods during the trial period and for 8 weeks after the last administration of the trial medication or have undergone surgical sterilization; 9.The subject voluntarily participates in this study, signs the informed consent form, has good compliance, and cooperates with follow-up.

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Exclusion Criteria:

1. Patients with central nervous system involvement;
2. History or concurrent other untreated malignant tumors, except for cured basal cell carcinoma of the skin, cervical carcinoma in situ, and superficial bladder cancer;
3. Patients with the following cardiovascular diseases: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval for males ≥450 ms, for females ≥470 ms); Class III to IV heart failure according to NYHA standards, or echocardiography indicating left ventricular ejection fraction (LVEF) \<50%;
4. Coagulation abnormalities (INR \>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), with a tendency to bleed or undergoing thrombolytic or anticoagulant therapy;
5. Arterial/venous thrombotic events within 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
6. Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.);
7. Major surgical procedures or severe traumatic injuries, fractures, or ulcers within 4 weeks prior to enrollment;
8. Factors that significantly affect the absorption of oral medications, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
9. Active infections requiring antimicrobial treatment (e.g., requiring antibacterial, antiviral drugs, excluding chronic hepatitis B antiviral treatment, antifungal treatment);
10. Active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL) or hepatitis C (hepatitis C antibody positive, and HCV RNA above the lower limit of detection of the analytical method);
11. History of substance abuse and inability to quit or mental disorders;
12. Participation in other anticancer drug clinical trials within 4 weeks prior to enrollment;
13. Received treatment with potent CYP3A4 inhibitors within 7 days prior to enrollment, or received treatment with potent CYP3A4 inducers within 12 days prior to study participation;
14. Pregnant or breastfeeding women; patients of childbearing potential who are unwilling or unable to use effective contraceptive measures;
15. Other situations judged by the investigator that may affect the conduct of the clinical study and the determination of study results.

Where it's running

• The First Affiliated Hospital of Nanchang University
  Nanchang, Jiangxi, China Recruiting

Study contacts

• Principal investigator: Fei Li, professor — The First Affiliated Hospital of Nanchang University
• Study coordinator: Yulan Zhou Doctor, PhD
• Email: wenxin_yl@163.com
• Phone: 86-0791-88692743

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Orelabrutinib plus rituximab with optional lenalidomide for untreated marginal zone lymphoma using a response-adapted plan

  This will test whether giving orelabrutinib with rituximab, and adding lenalidomide for those who don't fully respond, helps people with newly diagnosed marginal zone lymphoma achieve complete remissions.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07448324

• Orelabrutinib plus zebetuzumab and lenalidomide vs bendamustine‑rituximab for newly diagnosed marginal zone lymphoma

  This study will test whether a combination of orelabrutinib, zebetuzumab, and lenalidomide helps people with newly diagnosed marginal zone lymphoma compared with a standard bendamustine plus rituximab regimen.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07208981

• First-line treatment with orelabrutinib plus rituximab for marginal zone lymphoma

  This will test whether taking orelabrutinib together with rituximab works and is safe as a first systemic treatment for adults with marginal zone lymphoma.

  Recruiting at 18 sites Phase 2 Second Affiliated Hospital, Zhejiang University, School of Medicine · Hangzhou, Zhejiang and 17 other locations · NCT07022223

• Orelabrutinib plus Pola-R-CHP as first-line treatment for intermediate- to high-risk DLBCL

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  Recruiting at 2 sites The First Affiliated Hospital of Xiamen University · Xiamen, Fujian and 1 other locations · NCT07778212

• PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib for newly diagnosed primary or secondary CNS lymphoma

  This trial will test whether combining a PD‑1 blocker with rituximab, high‑dose methotrexate, and orelabrutinib helps people with newly diagnosed primary or secondary central nervous system diffuse large B‑cell lymphoma.

  Recruiting Phase 2 The First Affiliated Hospital with Nanjing Medical University · Nanjing, Jiangsu · NCT07410520

• Orelabrutinib alone or with a CD20 antibody for people newly diagnosed with marginal zone lymphoma

  This trial tests if orelabrutinib by itself or together with a CD20 antibody can treat adults who have just been diagnosed with marginal zone lymphoma.

  Recruiting Phase 4 Beijing Tongren Hospital · Beijing and 2 other locations · NCT07355699

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.