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

Study Overview
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Brief Summary
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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.

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

Conditions
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Refractory/Relapsed Autoimmune Hemolytic Anemia

Intervention / Treatment
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* Drug: Zanubrutinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events and severe adverse events |  | within 24 weeks | 
| Relapse free survival rate |  | within 48 weeks |