Orelabrutinib after short-course R-CHOP for people with newly diagnosed marginal zone lymphoma

Orelabrutinib as Consolidation and Maintenance Therapy in Treatment-Naïve Marginal Zone Lymphoma: A Study of Efficacy and Safety.

This treatment plan will try whether taking orelabrutinib after three cycles of R-CHOP helps people with newly diagnosed marginal zone lymphoma stay in remission.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: orelabrutinib, Rituximab, chemotherapy
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT07372365 on ClinicalTrials.gov

What this trial studies

Adults with treatment‑naïve, CD20‑positive marginal zone lymphoma will be screened with blood tests, imaging, and health assessments to confirm eligibility. Enrolled participants receive three cycles of standard R‑CHOP chemotherapy and have their response evaluated. Those with a good response proceed to three cycles of consolidation with orelabrutinib plus rituximab, followed by ongoing orelabrutinib maintenance. Safety, tolerability, and duration of response will be monitored throughout treatment and follow‑up.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed, CD20‑positive marginal zone lymphoma who require systemic treatment, have ECOG performance status ≤2, and meet organ function criteria are ideal candidates.

Not a fit: People who already received systemic therapy, who have inadequate cardiac or renal function outside the study limits, or who are unable or unwilling to take an oral targeted agent may not benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could prolong remission and reduce the need for extended chemotherapy in people with marginal zone lymphoma.

How similar studies have performed: Bruton tyrosine kinase inhibitors have shown activity in marginal zone lymphoma and rituximab regimens are effective, but using orelabrutinib specifically as consolidation and maintenance is a relatively new strategy.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed CD20-positive marginal zone lymphoma (MZL) that has not received systemic therapy.
2. MZL that has progressed or relapsed after prior local therapy (local therapy includes surgery, radiotherapy, Helicobacter pylori eradication, and hepatitis C treatment) or is not amenable to local therapy.
3. Age ≥18 years.
4. Presence of an indication for treatment as determined by the investigator or patient's willingness to receive treatment.
5. Eastern Cooperative Oncology Group (ECOG) performance status score ≤2.
6. Adequate organ function as defined below:

   * Hematology: Hemoglobin (HB) ≥60 g/L, platelets (PLT) ≥50×10⁹/L, neutrophils (NE) ≥1.0×10⁹/L (Note: Subjects with cytopenia due to lymphoma bone marrow involvement are not restricted by this criterion).
   * Cardiac: Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiogram.
   * Renal: Creatinine ≤1.5×upper limit of normal (ULN) or creatinine clearance ≥30 ml/min.
   * Hepatic: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×ULN.
7. Women of childbearing potential must have a negative pregnancy test. Both male and female patients must agree to use effective contraception during the treatment period and for 2 years thereafter.
8. Life expectancy of more than 3 months.
9. Voluntary provision of written informed consent.

Exclusion Criteria:

1. Underwent major surgery or severe trauma within 2 weeks prior to enrollment, or has not yet recovered from significant adverse effects.
2. Has other malignancies currently or within the past 3 years, excluding those that have been cured (such as basal or squamous cell carcinoma of the skin, superficial bladder cancer, prostatic intraepithelial neoplasia, and cervical carcinoma in situ).
3. Has a history of stroke or intracranial hemorrhage within the past 3 months.
4. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
5. Has evidence of any comorbidities or medical conditions that may interfere with the conduct of the study or place the patient at significant risk, including but not limited to severe cardiovascular disease (e.g., New York Heart Association class III or IV heart disease, myocardial infarction within the past 6 months, unstable arrhythmia, or unstable angina) and/or severe pulmonary disease (e.g., severe obstructive pulmonary disease and a history of symptomatic bronchospasm).
6. Is infected with human immunodeficiency virus, or has uncontrollable active hepatitis C virus or hepatitis B virus infection.
7. Has uncontrollable active infection.
8. Is pregnant or breastfeeding.
9. Has any life-threatening disease, medical condition, or organ dysfunction that may jeopardize the safety of the patient, as determined by the investigator.
10. Has any condition that may interfere with the absorption or metabolism of orelabrutinib or place the study results at unnecessary risk.
11. Has central nervous system involvement by marginal zone lymphoma or evidence of disease transformation.
12. Has any condition that the investigator judges may interfere with the patient's full participation in the study; any condition that poses significant risk to the patient; or any condition that may interfere with the interpretation of study data.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Conditions Marginal Zone Lymphoma