NCT07441993

Exploratory Study of Orelabrutinib in the Treatment of Early-stage Untreated MZL

Orelabrutinib for the Treatment of Marginal Zone Lymphoma: A Phase II, Multicenter, Open-label Study

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-arm, multicenter, prospective, phase II study. The primary objective is to assess the efficacy and safety of orelabrutinib in treatment-naïve patients with marginal zone lymphoma.

Detailed description

Marginal zone lymphoma (MZL) is a group of indolent B-cell malignancies originating from B lymphocytes, primarily occurring in the marginal zones of the spleen, lymph nodes, and mucosa-associated lymphoid tissues. Its histological features are characterized by abnormal proliferation of marginal zone cells surrounding lymphoid follicles. The Bruton tyrosine kinase (BTK) signaling pathway plays a critical role in B-cell receptor-mediated signal transduction and is significant in the development and progression of various B-cell malignancies. Ibrutinib, as the first BTK inhibitor, has demonstrated remarkable efficacy in the treatment of B-cell lymphomas. However, its poor kinase selectivity leads to a high incidence of off-target toxicities, including thrombocytopenia, neutropenia, bleeding, fatigue, rash, and atrial fibrillation in clinical settings, which limits its long-term use. Orelabrutinib is a highly selective oral small-molecule BTK inhibitor belonging to the nicotinamide class of compounds. It covalently binds to BTK and represents a new generation of selective irreversible BTK inhibitors. Due to its higher selectivity for BTK and favorable safety profile observed in previous human studies, orelabrutinib holds promise as a superior therapeutic option for B-cell malignancies. To further improve clinical outcomes for MZL patients, there is an urgent need to explore treatment strategies with better efficacy and lower toxicity. This study aims to evaluate the efficacy and safety of orelabrutinib in previously untreated localized-stage MZL patients, providing new therapeutic evidence for this population. This study is a multicenter, prospective trial involving previously untreated patients with MZL. During the induction phase (cycles 1-6), patients will receive orelabrutinib 150 mg, administered in 28-day treatment cycles. Following completion of the induction phase, patients will be followed during a post-treatment follow-up period.

Conditions

• Marginal Zone Lymphoma

Interventions

Type	Name	Description
DRUG	Orelabrutinib	Induction phase (cycle 1-6): Orelabrutinib (150 mg)

Timeline

• Start date: 2026-01-05
• Primary completion: 2027-12-01
• Completion: 2028-12-01
• First posted: 2026-03-02
• Last updated: 2026-03-02

Locations

14 sites across 1 country: China