Orelabrutinib Combined With Zebetuzumab and Lenalidomide for the Treatment of Newly Diagnosed MZL

NCT ID: NCT07208981

Last Updated: 2025-10-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 169 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-14
• Study Completion Date: 2031-06-01

Brief Summary

This is an open-label, multicenter, phase 2, non-randomized study aiming to evaluate the efficacy and safety of orelabrutinib combined with zebetuzumab and lenalidomide or bendamustine combined with rituximab in the treatment of newly diagnosed marginal zone lymphoma (MZL).

Conditions

Marginal Zone Lymphoma(MZL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group of orelabrutinib combined with zebetuzumab and lenalidomide

Group Type: EXPERIMENTAL

Orelabrutinib

Intervention Type: DRUG

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Maintenance phase (a total of 24 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Patients who achieve complete remission (CR) or partial remission (PR) after 6 cycles will decide whether to undergo maintenance therapy based on the investigator's choice.

Zebetuzumab

Intervention Type: DRUG

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Zebetuzumab (375 mg/m2, d1/C1-C6).

Lenalidomide

Intervention Type: DRUG

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Lenalidomide (20 mg, d1-d21).

Group of bendamustine combined with rituximab

Group Type: ACTIVE_COMPARATOR

Bendamustine + Rituximab

Intervention Type: DRUG

Treatment period (a total of 6 cycles, each cycle lasting 28 days), Bendamustine (90 mg/m2, d1-2), Rituximab (375 mg/m2, d1/C1-6).

Interventions

Orelabrutinib

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Maintenance phase (a total of 24 cycles, each cycle lasting 28 days), Orelabrutinib (150 mg, d1-d28). Patients who achieve complete remission (CR) or partial remission (PR) after 6 cycles will decide whether to undergo maintenance therapy based on the investigator's choice.

Intervention Type: DRUG

Zebetuzumab

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Zebetuzumab (375 mg/m2, d1/C1-C6).

Intervention Type: DRUG

Lenalidomide

Induction treatment phase (a total of 6 cycles, each cycle lasting 28 days), Lenalidomide (20 mg, d1-d21).

Intervention Type: DRUG

Bendamustine + Rituximab

Treatment period (a total of 6 cycles, each cycle lasting 28 days), Bendamustine (90 mg/m2, d1-2), Rituximab (375 mg/m2, d1/C1-6).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. Age 18-75 years, gender not restricted;
• 2. Histopathologically confirmed CD20-positive marginal zone lymphoma includes MALT, SMZL, and NMZL; at least one measurable lesion;
• 3. Indication for treatment

• 3.3. Recommended indications for the treatment of newly diagnosed SMZL. Including: ① Progressive or painful splenomegaly; ② Symptomatic or progressive cytopenia such as HB<100g/L, PLT<80×10^9/L, absolute neutrophil count (ANC)<1.0×10^9/L (note to differentiate from cytopenia caused by autoimmune factors);
• 4. Without prior systemic treatment, may include MZL (marginal zone lymphoma) that has progressed, relapsed, or is unsuitable for local treatment after previous local therapy (local treatment includes surgery, radiotherapy, anti-Helicobacter pylori therapy for at least 12 months, or anti-hepatitis C therapy);
• 5. ECOG performance status score 0-2 points
• 6. The main organ functions meet the following criteria (except for SMZL, which is judged separately by the investigator to meet treatment requirements): Complete blood count: Absolute neutrophil count ≥1.5×10^9/L, platelets ≥75×10^9/L, hemoglobin ≥75g/L; if accompanied by bone marrow involvement, absolute neutrophil count ≥1.0×10^9/L, platelets ≥50×10^9/L, hemoglobin ≥50g/L; Blood biochemistry: Total bilirubin ≤ 1.5 times ULN, AST or ALT ≤ 2 times ULN; serum creatinine ≤ 1.5 times ULN; serum amylase ≤ ULN; creatinine clearance rate ≥ 60 mL/min;
• 7. Coagulation function: International Normalized Ratio (INR) ≤1.5 times ULN;
• 8. Expected survival time ≥ 12 months;
• 9. Voluntarily sign a written informed consent before trial screening.

Exclusion Criteria

• 1. Currently or previously diagnosed with other malignancies, unless radical treatment has been performed and there is evidence of no recurrence or metastasis within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, and localized squamous cell carcinoma of the skin;
• 2. Lymphoma involving the central nervous system or transforming to a higher grade;
• 3. Uncontrolled or significant cardiovascular diseases, including: a) Occurrence of New York Heart Association (NYHA) Class III-IV congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first administration of the investigational drug, or the presence of treatable arrhythmias at screening, with left ventricular ejection fraction (LVEF) <50%; b) Primary cardiomyopathies (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, unclassified cardiomyopathy); c) A clinically significant history of QTc interval prolongation, or QTc interval during the screening period >470ms for females and >450ms for males; d) Subjects with symptomatic or medication-requiring coronary heart disease; e) Suffering from uncontrolled hypertension (blood pressure remains uncontrolled after more than one month of using a reasonable and tolerable dosage of three or more antihypertensive drugs (including diuretics) based on lifestyle improvements, or blood pressure can only be effectively controlled by taking four or more antihypertensive drugs);
• 4. Active bleeding within 2 months prior to screening, or currently taking anticoagulants, or deemed by the investigator to have a clear bleeding tendency;
• 5. History of deep vein thrombosis or pulmonary embolism in the past six months;
• 6. Underwent major surgery within 6 weeks prior to screening or minor surgery within 2 weeks prior to screening. Major surgery refers to procedures performed under general anesthesia, but endoscopic examinations for diagnostic purposes are not considered major surgery. The insertion of vascular access devices is exempt from this exclusion criterion;
• 7. Active infection or uncontrolled HBV (HBsAg positive and/or HBcAb positive with HBV DNA titer positive), HCV RNA positive, HIV/AIDS, or other severe infectious diseases;
• 8. Currently, there are subjects with severe pulmonary function impairment due to conditions such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, and drug-related pneumonia: FEV1% or DLCO (or DLCO/VA) %pred < 40% (with severe pulmonary ventilation and gas exchange dysfunction);
• 9. Pregnant, lactating women and childbearing age subjects unwilling to use contraception;
• 10. Need to continuously take medications with moderate to strong inhibitory or strong inducing effects on cytochrome P450 CYP3A;
• 11. The investigator considers other conditions unsuitable for participating in this trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province Hospital

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianyong Li, PhD, MD

Role: CONTACT

lijianyonglm@126.com

86-13951877733

Huayuan Zhu, PhD, MD

Role: CONTACT

huayuan.zhu@hotmail.com

86-13813810650

Facility Contacts

Jianyong Li, PhD, MD

Role: primary

lijianyonglm@126.com

86-13951877733

Huayuan Zhu, PhD, MD

Role: backup

huayuan.zhu@hotmail.com

86-13813810650

Other Identifiers

Optional

Identifier Type: -

Identifier Source: org_study_id