The Safety and Efficacy of Zanubrutinib in Refractory/Relapsed Autoimmune Hemolytic Anemia

A Phase II, Single Center, Open-label Trial to Determine the Safety and Efficacy of Zanubrutinib in Refractory/Relapsed Autoimmune Hemolytic

The sample size of this study is calculated based on Simon's two-stage design. The first stage of the study enrolled a cohort of 12 patients. If after 12 weeks at least 6 patients achieved a response, then enrollment was expanded to a total of 26 patients. The null hypothesis was unaccepted if more than 14 of 26 patients achieved the response. Accounting for a 20% dropout rate, the estimated final sample size was 33 patients.

Study Overview

• Status: Recruiting
• Conditions: Refractory/Relapsed Autoimmune Hemolytic Anemia
• Intervention / Treatment: Drug: Zanubrutinib

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jingyu Zhao, MPH; Phone Number: 13752253515; Email: zhaojingyu@ihcams.ac.cn
• Study Contact Backup: Name: Weiwang Li, PhD; Phone Number: 15332132036; Email: liweiwang@ihcams.ac.cn

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300131
      • Recruiting
      • Regenerative Medicine Center
      • Contact: Jingyu Zhao; Phone Number: 13752253515; Email: zhaojingyu94@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age from 6 to 70
• Diagnosis of Coombs-negative AIHA
• Diagnosis of warm AIHA, mixed AIHA or Evans syndrome.
• Meets the criteria of relapsed / refractory AIHA
• ECOG ≤ 3
• Willing and able to comply with the requirements for this study and written informed consent.

Exclusion Criteria:

• Diagnosis of any of the following diseases: Cold agglutinin disease, cold agglutinin syndrome, mixed AIHA, paroxysmal cold hemoglobinuria (PCH).
• Diagnosis of active stage of connective tissue disease.
• History of lymphoproliferative tumors or any other malignant.
• Diagnosis of other inherited or acquired hemolytic diseases.
• Secondary AIHA caused by drugs or infection.
• Previously received organ or stem cell transplantation.
• History of thrombosis or organ infarction.
• Received rituximab within 8 weeks before enrollment.
• Previously treated with BTK inhibitor ≥ 2 weeks.
• Received low-molecular-weight heparin or warfarin within 1 week before enrollment and need to continue the drug treatment.
• Received CYP3A4 Enzyme Inhibitors or Inducers within 1 week before enrollment and need to continue the drug treatment.
• Uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment), known human immunodeficiency virus (HIV), known evidence of active infectious hepatitis B, and/or known evidence of active hepatitis C.
• Any severe and/or uncontrolled medical conditions: refractory hypertension, clinically significant cardiac diseases, renal diseases, liver diseases and metabolic diseases, etc.
• History of mental illness.
• Participation in another clinical trial within 4 weeks before the start of this trial.
• Pregnant or breast-feeding patients.
• Patients considered ineligible for the study by the investigator for reasons other than the above.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib; Each recruited subject will accept Zanubrutinib treatment.	Drug: Zanubrutinib; Zanubrutinib was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	The percentage of patients achieved complete response, complete response with incomplete hemolysis recovery, and partial response.	within 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Relapse free survival rate	within 48 weeks
Incidence of adverse events and severe adverse events	within 24 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China
• Investigators: Principal Investigator: Liwei Fang, MD, Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2023
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: August 27, 2023
• First Submitted That Met QC Criteria: August 27, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 26, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Anemia; Hemolysis; Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: IHBDH-IIT20230711

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No