Orelabrutinib for adults with early-stage untreated marginal zone lymphoma

Orelabrutinib for the Treatment of Marginal Zone Lymphoma: A Phase II, Multicenter, Open-label Study

This trial will try orelabrutinib, a selective oral BTK inhibitor, as first-line treatment for adults with stage I–II marginal zone lymphoma to see if it works and is safe.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (other)
• Drugs / interventions: radiation, orelabrutinib, Ibrutinib
• Locations: 14 sites (Guangzhou, Guangdong and 13 other locations)
• Trial ID: NCT07441993 on ClinicalTrials.gov

What this trial studies

This is a single-arm, multicenter, prospective phase II trial enrolling treatment‑naïve adults with histologically confirmed stage I–II marginal zone lymphoma. Participants receive oral orelabrutinib with scheduled clinical and laboratory monitoring to track response and adverse events. The study's primary objectives are to measure anti-lymphoma activity and safety in this population. Trial sites are located at major cancer centers across China.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed stage I or II marginal zone lymphoma who are treatment‑naïve, have ECOG 0–2, and meet the specified laboratory and organ-function criteria are ideal candidates.

Not a fit: Patients with central nervous system involvement, transformation to high‑grade lymphoma, uncontrolled significant cardiovascular disease, or inadequate blood/organ function are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, orelabrutinib could offer an effective first-line oral option for MZL with fewer off-target side effects than earlier BTK inhibitors.

How similar studies have performed: Earlier BTK inhibitors like ibrutinib have shown clear activity in B‑cell lymphomas but carry notable off‑target toxicities, while orelabrutinib has displayed favorable safety and activity in prior early studies though its first-line use in MZL remains novel.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years, regardless of gender;
2. Patients with histopathologically confirmed stage I/II marginal zone lymphoma;
3. ECOG performance status score of 0-2;
4. Major organ functions meeting the following criteria:

   1. Blood tests: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelets ≥75×10\^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow involvement, ANC ≥1.0×10\^9/L, platelets ≥50×10\^9/L, hemoglobin ≥50g/L;
   2. Blood biochemistry: Total bilirubin ≤1.5×ULN, AST or ALT ≤2×ULN; serum creatinine ≤1.5×ULN;
5. Coagulation function: International normalized ratio (INR) ≤1.5×ULN;
6. Expected survival time ≥12 months;
7. Voluntary written informed consent signed before trial screening.

Exclusion Criteria:

1. Lymphoma involving the central nervous system or transformation to high-grade;
2. Uncontrolled or significant cardiovascular diseases, including:

   1. New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first dose of the study drug, or arrhythmia requiring treatment at screening, with left ventricular ejection fraction (LVEF) \<50%;
   2. Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, or unclassified cardiomyopathy);
   3. History of clinically significant QTc interval prolongation, or QTc interval \>470 ms for females or \>450 ms for males at screening;
   4. Subjects with symptomatic coronary artery disease requiring medication;
   5. Poorly controlled hypertension (failure to achieve target blood pressure after at least one month of lifestyle modification and treatment with three or more antihypertensive drugs, including diuretics, at maximally tolerated doses, or requiring four or more antihypertensive drugs for effective control).
3. Active bleeding within 2 months prior to screening, or current use of anticoagulants, or investigator-determined clear bleeding tendency;
4. History of deep vein thrombosis or pulmonary embolism within the past six months;
5. Urine protein ≥2+ and 24-hour urine protein quantification ≥2 g/24 hours;
6. Clinically significant gastrointestinal abnormalities that may affect drug intake, transport, or absorption (e.g., inability to swallow, chronic diarrhea, intestinal obstruction), or subjects with total gastrectomy;
7. Current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or other conditions affecting lung function;
8. Pregnant or breastfeeding women, or subjects of childbearing potential unwilling to use contraception;
9. Continuous use of drugs with moderate to strong cytochrome P450 CYP3A inhibition or strong induction effects;
10. Other conditions deemed by the investigator as unsuitable for participation in this trial.

Where this trial is running

Guangzhou, Guangdong and 13 other locations

• Nanfang Hospital, Southern Medical University — Guangzhou, Guangdong, China (RECRUITING)
• Henan Cancer Hospital — Zhengzhou, Henan, China (RECRUITING)
• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (RECRUITING)
• Xiangyang Central Hospital — Xiangyang, Hubei, China (RECRUITING)
• The Second Xiangya Hospital of Central South University — Changsha, Hunan, China (RECRUITING)
• Jiangsu Province People's Hospital — Nanjing, Jiangsu, China (RECRUITING)
• Affiliated Hospital of Nantong University — Nantong, Jiangsu, China (RECRUITING)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (RECRUITING)
• The First Bethune Hospital of Jilin University — Changchun, Jilin, China (RECRUITING)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (RECRUITING)
• Shandong Cancer Hospital & Institute — Jinan, Shandong, China (RECRUITING)
• Shandong Provincial Hospital — Jinan, Shandong, China (RECRUITING)
• Beijing Tongren Hospital, Capital Medical University — Beijing, China (RECRUITING)
• Hematology Hospital, Chinese Academy of Medical Sciences — Tianjin, China (RECRUITING)

Study contacts

• Principal investigator: Shuhua yi — Hematology Hospital, Chinese Academy of Medical Sciences
• Study coordinator: Shuhua Yi

Conditions: Marginal Zone Lymphoma, Lymphoma, Marginal zone lymphoma, Orelabrutinib