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

A Single-arm, Prospective Clinical Study to Evaluate the Efficacy and Safety of Orelabrutinib Combined With Rituximab as First-line Systemic Treatment 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.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: radiation, rituximab, orelabrutinib, chemotherapy
• Locations: 18 sites (Hangzhou, Zhejiang and 17 other locations)
• Trial ID: NCT07022223 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm Phase 2 study enrolling adults with CD20-positive marginal zone lymphoma to receive orelabrutinib combined with rituximab as first-line systemic therapy. All participants receive induction treatment with the combination given in 28-day cycles, and investigators will monitor tumor response and side effects during and after treatment. The trial focuses on patients who need systemic therapy or who have progressed after local treatments and documents hematologic, biochemical, and clinical outcomes. Safety monitoring will include regular blood counts and organ-function tests to detect adverse events.

Who should consider this trial

Good fit: Adults (≥18 years) with histologically confirmed CD20-positive marginal zone lymphoma (MALT, SMZL, or NMZL) who have measurable lesions >1.5 cm outside the spleen, require systemic treatment or have progressed after local therapy, and have ECOG 0–2 with adequate organ function are the intended candidates.

Not a fit: Patients with poor organ function, ECOG performance >2, severe cytopenias below inclusion thresholds, other active malignancies, or lymphoma subtypes outside CD20-positive MZL are unlikely to benefit from joining this protocol.

Why it matters

Potential benefit: If successful, the chemo-free combination could produce meaningful responses while lowering the high rates of severe toxicity seen with intensive immunochemotherapy.

How similar studies have performed: Other BTK inhibitors and anti-CD20 antibodies have shown activity in MZL, but the specific combination of orelabrutinib plus rituximab as first-line systemic therapy is a relatively new approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years, regardless of gender;
* Histologically confirmed CD20-positive marginal zone lymphoma, including MALT, SMZL, and NMZL, with at least one lesion outside the spleen measuring more than 1.5 cm in any axis;
* MZL that has progressed or relapsed after prior local therapy (including surgery, radiotherapy, anti-Helicobacter pylori treatment, and anti-hepatitis C treatment), or is not suitable for local therapy;
* ECOG performance status of 0-2;
* Presence of an indication for treatment as judged by the investigator (symptomatic, cytopenia, risk of end-organ damage, bulky disease, ongoing progression, or patient's desire for treatment);
* Adequate function of major organs, as follows:
* Hematology: Absolute neutrophil count ≥ 1.5×109/L, platelets ≥ 75×109/L, hemoglobin ≥ 75 g/L; if there is bone marrow involvement, absolute neutrophil count ≥ 1.0×109/L, platelets ≥ 50×109/L, hemoglobin ≥ 50 g/L;
* Biochemistry: Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), AST or ALT ≤ 2 times ULN; serum creatinine ≤ 1.5 times ULN; serum amylase ≤ ULN;
* Coagulation: International normalized ratio (INR) ≤ 1.5 times ULN.
* Life expectancy of ≥ 3 months;
* Voluntary written informed consent obtained before screening for the trial.

Exclusion Criteria:

* Currently or previously having other malignancies, unless there is evidence of no recurrence or metastasis within the past 5 years after curative treatment;
* Lymphoma involvement of the central nervous system or transformation to high-grade lymphoma;
* Non-hematological toxicities from prior anti-cancer treatments not recovered to ≤ Grade 1 (excluding alopecia);
* Presence of uncontrolled or significant cardiovascular disease, including:
* New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months before the first administration of the study drug, or arrhythmias requiring treatment at screening, left ventricular ejection fraction (LVEF) \< 50%;
* Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy);
* History of clinically significant QTc interval prolongation, or QTc interval \> 470 ms for females, \> 450 ms for males during the screening period;
* Symptomatic or medically treated coronary artery disease;
* Uncontrolled hypertension (defined as blood pressure not reaching target levels despite a reasonable and tolerable full dose of three or more antihypertensive drugs (including diuretics) for more than one month, or requiring four or more antihypertensive drugs to effectively control blood pressure).
* Active bleeding within 2 months before screening, or currently taking anticoagulant drugs, or deemed by the investigator to have a clear tendency to bleed;
* Urine protein ≥ 2+, and 24-hour urine protein quantification ≥ 2 g/24 hours;
* History of deep vein thrombosis or pulmonary embolism within the past six months;
* History of organ transplantation or allogeneic bone marrow transplantation;
* Major surgery within 6 weeks before screening or minor surgery within 2 weeks before screening. Major surgery is defined as surgery using general anesthesia, but diagnostic endoscopy is not considered major surgery. Insertion of a vascular access device will be exempt from this exclusion criterion;
* Active infection or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA titer), HCV Ab positive, HIV/AIDS, or other severe infectious diseases;
* Currently having pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or other conditions that significantly affect pulmonary function;
* Previous treatment with BTK, BCR pathway inhibitors (such as PI3K, Syk), or BCL-2 inhibitors;
* Suitable and preparing for stem cell transplantation;
* Any psychiatric or cognitive impairment that may limit their understanding, execution of the informed consent form, and compliance with the study;
* Subjects with drug abuse or alcoholism;
* Pregnant, breastfeeding women, and fertile subjects unwilling to use contraception;
* Need to continuously take drugs with moderate to severe inhibitory or strong inducing effects on cytochrome P450 CYP3A;
* Any other condition deemed by the investigator as unsuitable for participation in this trial.

Where this trial is running

Hangzhou, Zhejiang and 17 other locations

• Second Affiliated Hospital, School of Medicine, Zhejiang University — Hangzhou, Zhejiang, China (Recruiting)
• Dongyang People's Hospital — Dongyang, China (Recruiting)
• Affiliated Hangzhou First People's Hospital — Hangzhou, China (Recruiting)
• Zhejiang cancer Hospital — Hangzhou, China (Recruiting)
• Huzhou Central Hospital — Huzhou, China (Recruiting)
• Affiliated Hospital of Jiaxing University — Jiaxing, China (Recruiting)
• The Second Affiliated Hospital of Jiaxing University — Jiaxing, China (Recruiting)
• Lishui central Hospital — Lishui, China (Recruiting)
• the Affiliated Peopele'S Hospital of Ningbo University — Ningbo, China (Recruiting)
• Quzhou People's Hospital — Quzhou, China (Recruiting)
• Shaoxing Central Hospital — Shaoxing, China (Recruiting)
• shaoxing People's Hospital — Shaoxing, China (Recruiting)
• Taizhou Central Hospital — Taizhou, China (Recruiting)
• Taizhou First People's Hospital — Taizhou, China (Recruiting)
• Taizhou Hospital ofzhejiang Province — Taizhou, China (Recruiting)
• The Second Affiliated Hospital and Yuying childrens Hospital of Wenzhou Medical University — Wenzhou, China (Recruiting)
• Yuyao People's Hospital — Yuyao, China (Recruiting)
• Affiliated Zhuji Hospital ofWenzhou Medical University — Zhuji, China (Recruiting)

Study contacts

• Study coordinator: yun Liang

Conditions Marginal Zone Lymphoma