Orelabrutinib Combined With Rituximab ± Lenalidomide in Response-Adapted Stratified Therapy for Untreated MZL

NCT07448324 | Recruiting Phase 2

• 1 other identifier: 2025-SR-258
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-arm, phase II study aimed at evaluating the safety and efficacy of orelabrutinib combined with rituximab ± lenalidomide in response-adapted stratified therapy for untreated marginal zone lymphoma. The primary endpoint is the complete response rate (CRR).

Conditions

Marginal Zone Lymphoma(MZL)

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  CRR is defined as the proportion of patients with complete response

  At the end of cycle 12 (each cycle is 21 days)

Secondary Outcomes (3)

• Overall response rate (ORR)

  At the end of cycle 12(each cycle is 21 days)

• 2 years Progression free survival (PFS)

  From date of signing the informed consent until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

• 2 years overall survival (OS)

  From date of signing the informed consent until the date of death from any cause, whichever came first, assessed up to 2 years

Study Arms (1)

Orelabrutinib Combined with Rituximab ± Lenalidomide

EXPERIMENTAL

Drug: Orelabrutinib; Drug: Rituximab; Drug: Lenalidomide

Interventions

Orelabrutinib DRUG

Orelabrutinib: 150mg qd C1-C6

Orelabrutinib Combined with Rituximab ± Lenalidomide

Rituximab DRUG

Rituximab: C1-C6

Orelabrutinib Combined with Rituximab ± Lenalidomide

Lenalidomide DRUG

After 6 cycles of orelabrutinib + rituximab CR: Continue orelabrutinib + rituximab for 6 cycles. PR/SD: Switch to orelabrutinib + rituximab + lenalidomide for 6 cycles. PD: Discontinue study treatment.

Orelabrutinib Combined with Rituximab ± Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Aged ≥18 years, either sex.
• Histopathologically confirmed CD20-positive marginal zone lymphoma (including MALT, SMZL, and NMZL) with at least 1 measurable lesion.
• Stage III or IV disease with an indication for treatment.
• No prior systemic therapy. Patients may have received prior local treatment (including surgery, radiotherapy, anti-Helicobacter pylori therapy, or anti-hepatitis C therapy) if they subsequently progressed, relapsed, or were unsuitable for local therapy.
• ECOG performance status of 0-2.
• Adequate organ function meeting the following criteria:
• Blood count: Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥75×10⁹/L, hemoglobin ≥75 g/L. If bone marrow involvement is present: absolute neutrophil count ≥1.0×10⁹/L, platelets ≥50×10⁹/L, hemoglobin ≥50 g/L.
• Blood chemistry: Total bilirubin ≤1.5×ULN, AST or ALT ≤2×ULN; serum creatinine ≤1.5×ULN; serum amylase ≤ULN.
• Coagulation: International normalized ratio (INR) ≤1.5×ULN.
• Expected survival ≥12 months.
• Voluntary provision of written informed consent before trial screening.

You may not qualify if:

• Current or history of other malignancies, unless treated with curative intent and without evidence of recurrence or metastasis within the past 5 years.
• Central nervous system involvement or transformation to high-grade lymphoma.
• Uncontrolled or significant cardiovascular diseases, including:
• New York Heart Association (NYHA) Class II or higher congestive heart failure, unstable angina, myocardial infarction within 6 months prior to the first study drug dose, or arrhythmia requiring treatment at screening; left ventricular ejection fraction (LVEF) \<50%.
• Primary cardiomyopathy (e.g., dilated, hypertrophic, arrhythmogenic right ventricular, restrictive, or unclassified cardiomyopathy).
• History of clinically significant QTc interval prolongation, or QTc interval \>470 ms (female) or \>450 ms (male) at screening.
• Symptomatic coronary artery disease or subjects requiring medication for it.
• Poorly controlled hypertension (defined as failure to achieve target blood pressure after ≥1 month of lifestyle modification combined with an adequate, tolerable regimen of ≥3 antihypertensive drugs including a diuretic, or requiring ≥4 antihypertensive drugs for control).
• Active bleeding within 2 months prior to screening, current use of anticoagulants, or any condition deemed by the investigator to indicate a clear bleeding tendency.
• History of deep vein thrombosis or pulmonary embolism within the past 6 months.
• History of organ transplantation or allogeneic bone marrow transplantation.
• Major surgery within 6 weeks or minor surgery within 2 weeks prior to screening. Major surgery requires general anesthesia (diagnostic endoscopy excluded). Insertion of vascular access devices is exempt.
• Active infection or uncontrolled HBV (HBsAg positive and/or HBcAb positive with positive HBV DNA), HCV Ab positive, HIV/AIDS, or other serious infectious diseases. (Active infection is defined as requiring systemic antimicrobial therapy or associated with systemic signs/symptoms of inflammation.)
• Current conditions severely impairing pulmonary function, such as pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, or drug-related pneumonia.
• Prior treatment with BTK inhibitors, BCR pathway inhibitors (e.g., PI3K, Syk inhibitors), or BCL-2 inhibitors.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

orelabrutinib; Rituximab; Lenalidomide

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; 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

Central Study Contacts

Lei Fan, PhD, MD

CONTACT

+86 13813976136; fanlei3014@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2026
• First Posted: March 4, 2026
• Study Start: April 1, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030
• Last Updated: March 4, 2026

Record last verified: 2025-04

Locations

CN (1)