RecruitingPhase 2NCT07448324

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

Orelabrutinib Combined With Rituximab ± Lenalidomide in Response-Adapted Stratified Therapy for Untreated MZL#a Prospective Single Arm Trial

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Enrollment

50 participants

Start Date

Apr 1, 2025

Study Type

INTERVENTIONAL

Conditions

Marginal Zone Lymphoma (MZL)

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).

Eligibility

Min Age: 18 Years

Inclusion Criteria11

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.

Exclusion Criteria18

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.
Pregnancy, lactation, or unwillingness to use effective contraception in subjects of childbearing potential.
Concomitant use of moderate/strong cytochrome P450 CYP3A inhibitors or strong inducers.
Any other condition considered by the investigator to make the subject unsuitable for trial participation.

Interventions

DRUGOrelabrutinib

Orelabrutinib: 150mg qd C1-C6

DRUGRituximab

Rituximab: C1-C6

DRUGLenalidomide

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.