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

NCT07208981 | Recruiting Phase 2

• 1 other identifier: Optional
• Study Type: interventional
• Target: 169
• Locations: 1 country
• Sites: 1

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)

Outcome Measures

Primary Outcomes (1)

• 3-year PFS rate

  PFS is defined as the first dose of treatment to the date of first documented progression or date of death from any cause, whichever occurs first. 3-year PFS rate will be estimated by Kaplan-Meier.

  From the first dose of treatment to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 66 months.

Secondary Outcomes (8)

• Overall response rate (ORR)

  On Day 1 of Cycle 4, Day 1 of Cycle 7, Day 1 of Cycle 13, Day 1 of Cycle 19, Day 1 of Cycle 25, Day 1 of Cycle 31 (each cycle is 28 days).

• Rate of best overall response (BOR)

  On Day 1 of Cycle 4, Day 1 of Cycle 7, Day 1 of Cycle 13, Day 1 of Cycle 19, Day 1 of Cycle 25, Day 1 of Cycle 31 (each cycle is 28 days).

• Time to response (TTR)

  On Day 1 of Cycle 4, Day 1 of Cycle 7, Day 1 of Cycle 13, Day 1 of Cycle 19, Day 1 of Cycle 25, Day 1 of Cycle 31 (each cycle is 28 days).

• Progression-free survival (PFS) rate

  From the first dose of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 66 months.

• Overall survival (OS) rate

  From the first dose of treatment until the date of death from any cause, assessed up to 66 months.

Study Arms (2)

Group of orelabrutinib combined with zebetuzumab and lenalidomide

EXPERIMENTAL

Drug: Orelabrutinib; Drug: Zebetuzumab; Drug: Lenalidomide

Group of bendamustine combined with rituximab

ACTIVE COMPARATOR

Drug: Bendamustine + Rituximab

Interventions

Orelabrutinib 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.

Group of orelabrutinib combined with zebetuzumab and lenalidomide

Zebetuzumab DRUG

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

Group of orelabrutinib combined with zebetuzumab and lenalidomide

Lenalidomide DRUG

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

Group of orelabrutinib combined with zebetuzumab and lenalidomide

Bendamustine + Rituximab 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).

Group of bendamustine combined with rituximab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age 18-75 years, gender not restricted;
• \. Histopathologically confirmed CD20-positive marginal zone lymphoma includes MALT, SMZL, and NMZL; at least one measurable lesion;
• \. Indication for treatment
• 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);
• \. 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);
• \. ECOG performance status score 0-2 points
• \. 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;
• \. Coagulation function: International Normalized Ratio (INR) ≤1.5 times ULN;
• \. Expected survival time ≥ 12 months;
• \. Voluntarily sign a written informed consent before trial screening.

You may not qualify if:

• \. 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;
• \. Lymphoma involving the central nervous system or transforming to a higher grade;
• \. 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);
• \. Active bleeding within 2 months prior to screening, or currently taking anticoagulants, or deemed by the investigator to have a clear bleeding tendency;
• \. History of deep vein thrombosis or pulmonary embolism in the past six months;
• \. 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;
• \. 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);
• \. Pregnant, lactating women and childbearing age subjects unwilling to use contraception;
• \. Need to continuously take medications with moderate to strong inhibitory or strong inducing effects on cytochrome P450 CYP3A;
• \. The investigator considers other conditions unsuitable for participating in this trial.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

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

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

orelabrutinib; Lenalidomide; Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Butyrates; Acids, Acyclic; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Jianyong Li, PhD, MD

CONTACT

86-13951877733; lijianyonglm@126.com

Huayuan Zhu, PhD, MD

CONTACT

86-13813810650; huayuan.zhu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2025
• First Posted: October 6, 2025
• Study Start: August 14, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2031
• Last Updated: October 6, 2025

Record last verified: 2025-08

Locations

CN (1)