Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA

Status Recruiting

Clinical Trial Summary

Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disorder characterized by the destruction of red blood cells through warm or cold antibodies. Glucocorticoid (combined with rituximab) is the first-line treatment. However, the recurrence rate is very high and some patients may not respond to steroids. Second-line therapies include cyclosporine A (CsA), cyclophosphamide, rituximab, azathioprine, and even splenectomy. Bruton's tyrosine kinase (BTK) plays a crucial role in the signaling pathway of B-cell receptor (BCR), and has been found to be a major source of pathogenic signal transduction for various lymphoproliferative malignancies. The activity of BTK is related to the occurrence and progression of various B-cell lymphomas. Currently, BTK inhibitors are widely used in the treatment of B-cell lymphomas, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), and other B-cell lymphomas, showing significant efficacy. BTK affects the production of messenger molecules and regulates the BCR signaling pathway, causing B cells to transform into self-reactive B cells, which can trigger autoimmune diseases. Current research has shown that BTK activity increases in several autoimmune diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) . Therefore, BTK inhibitors (BTKi) are important for the treatment of autoimmune diseases. Ibrutinib, one kind of BTKi, has been proven to treat secondary autoimmune hemolytic anemia (AIHA) in CLL and control CLL progression, and is an effective drug for treating lymphoma-associated AIHA . One kind of second-generation selective BTKi, acalabrutinib, can also reduce the incidence of AIHA in relapsed or refractory CLL patients. Currently, phase-II clinical studies exploring the treatment of AIHA using Ibrutinib, acalabrutinib, and rilzabrutinib, another BTKi, are underway. Zanubrutinib (BGB-3111, Brukinsa®, BeiGene) is a second-generation irreversible BTKi developed by Chinese company BeiGene. Compared to Ibrutinib, zanubrutinib has shown stronger effective activity and higher selectivity towards BTK, and weaker effects on other targets such as TEC, EGFR, and Src families, with low off-target side effects. Its efficacy, durability, oral absorption, and targeting are better than those of Ibrutinib. Zanubrutinib is approved for the treatment of various B-cell lymphomas, and clinical trials have shown excellent efficacy and tolerability in CLL and WM patients. In previously treated CLL patients, zanubrutinib exhibits better efficacy and safety than Ibrutinib. Currently, phase II clinical studies of zanubrutinib in ITP, antiphospholipid syndrome, IgG4-related immune diseases, and active proliferative lupus nephritis are underway. The therapeutic effect of zanubrutinib on refractory warm autoimmune hemolytic anemia, is worth exploring through exploratory research.

Clinical Trial Description

n/a

Study Design

Related Conditions & MeSH terms

Clinical Trial Details

NCT number	NCT05922839
Study type	Interventional
Source	Peking Union Medical College Hospital
Contact	Miao Chen
Phone	+86 13520112578
Email	chenm@pumch.cn
Status	Recruiting
Phase	Phase 2
Start date	November 11, 2023
Completion date	December 2025

View Details

See also
Status	Clinical Trial	Phase
Recruiting	`NCT05786573` - A Study of Obexelimab in Patients With Warm Autoimmune Hemolytic Anemia (SApHiAre)	Phase 3
Withdrawn	`NCT03965624` - Efficacy and Safety of Ixazomib and Dexamethasone Refractory Autoimmune Cytopenia	Phase 2
Completed	`NCT01181154` - Rituximab in Auto-Immune Hemolytic Anemia	Phase 3
Recruiting	`NCT05925023` - Sirolimus in the Treatment of Refractory/Relapsed wAIHA	Phase 2
Recruiting	`NCT05757570` - An Open-label Study of Povetacicept in Subjects With Autoimmune Cytopenias	Phase 1/Phase 2
Withdrawn	`NCT04256148` - ALXN1830 in Patients With Warm Autoimmune Hemolytic Anemia	Phase 2
Terminated	`NCT03075878` - A Safety Study of SYNT001 in Participants With Warm Autoimmune Hemolytic Anemia (WAIHA)	Phase 1/Phase 2
Withdrawn	`NCT04956276` - Subcutaneous ALXN1830 in Adult Participants With Warm Autoimmune Hemolytic Anemia	Phase 2
Completed	`NCT03226678` - Study to Assess the Safety, Tolerability, Efficacy and PK of APL-2 in Patients With Warm Type Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD)	Phase 2
Recruiting	`NCT04119050` - Efficacy and Safety of M281 in Adults With Warm Autoimmune Hemolytic Anemia	Phase 2/Phase 3
Terminated	`NCT04253236` - To Assess the Efficacy and Safety of RVT-1401 in the Treatment of Warm Autoimmune Hemolytic Anemia (ASCEND-WAIHA).	Phase 2
Temporarily not available	`NCT05221619` - Post-trial Access for Nipocalimab in Participants With Warm Autoimmune Hemolytic Anemia (wAIHA)

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.