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.

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.