Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA

April 25, 2024 updated by: Chen Miao

Zanubrutinib in Relapsed or Refractory Warm Autoimmune Hemolytic Anemia: a Prospective Cohort Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Miao Chen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years.
  2. Confirmed diagnosis of wAIHA or Evans syndrome, primary or secondary to connective tissue disease. If it is secondary, there are no other treatment indications for systemic involvement of primary connective tissue disease.
  3. No response or relapse after glucocorticoid treatment.
  4. Baseline liver and kidney function (ALT, AST, Cr) is less than 2 times the normal range.
  5. Consent to sign the informed consent form.

Exclusion Criteria:

  1. Other important organ involvement in connective tissue disease.
  2. Uncontrolled infection or bleeding with standard treatment.
  3. Active HIV, HCV or HBV infection uncontrolled with standard treatment.
  4. Concurrent uncontrolled advanced malignant tumors or lymphoma.
  5. The subject is receiving any of the following drugs and has not met the following conditions of stable drug treatment duration at a fixed dose during screening: corticosteroids for at least 4 weeks; iron, vitamin B12 or folic acid for at least 4 weeks;
  6. Liver cirrhosis or portal hypertension.
  7. Pregnant or lactating women.
  8. Participation in other clinical trials within the last 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Zanubrutinib in the Treatment of Relapsed/Refractory wAIHA
Zanubrutinib 160mg, orally, twice daily, for a minimum of 3 months For effective patients, continue to use for 2 years after achieving optimal therapeutic effect.
Drug: Zanubrutinib
Zanubrutinib 160mg, orally, twice daily, for a minimum of 3 months, and for effective patients, continue to use for 2 years after achieving optimal therapeutic effect.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 3/6 months
ORR defined as the proportion of patients who met the criteria of either complete response (CR) or partial response (PR)
3/6 months
Complete response rate (CRR)
Time Frame: 3/6 months
CRR defined as the proportion of patients who met the criteria of complete response.
3/6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rate
Time Frame: 3/6 months
Relapse rate defined as the proportion of patients whose response shift from PR or CR to no response (NR).
3/6 months
Adverse events
Time Frame: 3/6 months
Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug.
3/6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chen Miao

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 20, 2023

First Submitted That Met QC Criteria

June 20, 2023

First Posted (Actual)

June 28, 2023

Study Record Updates

Last Update Posted (Actual)

April 26, 2024

Last Update Submitted That Met QC Criteria

April 25, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Zanubrutinib-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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