Efficacy of Daratumumab to Overcome Platelet Transfusion Refractoriness in Patients with Aplastic Anemia

Efficacy of Daratumumab to Overcome Platelet Transfusion Refractoriness in Patients with Aplastic Anemia

This is a phase 1, prospective, single-arm, open-label study. The aim of this study is to evaluate the transfusion responses of platelet increment by using Daratumumab among aplastic anemia patients with platelet transfusion refractoriness.

Inclusion Criteria:

• Diagnosis of aplastic anemia (AA)
• Dependent on platelet transfusions, characterized by either PLT<10×10^9/L, or PLT<20×10^9/L with bleeding events.
• Diagnosed with platelet transfusion refractoriness, characterized by Corrected count increment (CCI) <7500/ul at 60 min, or CCI <4500/ul at 24 hrs.
• Male or female age ≥ 12 years
• ECOG performance status ≤2
• Willing and able to comply with the requirements for this study and written informed consent.

Exclusion Criteria:

• The inherited bone marrow failure syndromes

• The presence of hemolytic PNH clone

• Combination of either radiotherapy or chemotherapy for solid tumors in recent 3 years, excluding the local tumor diagnosed 1 year ago and cured by surgical resection.

• Cytopenia caused by other diseases, including liver cirrhosis, active rheumatic connective tissue disease, and persistence of infectious diseases, etc.

• Uncontrolled infection

• HIV, HCV or HBV active infection

• The presence of any of the following bleeding events:

  • Gastrointestinal bleeding
  • Respiratory tract hemorrhage
  • Central nervous system bleeding

• Abnormal liver function: ALT or AST > 2 ULN, or TBil > 2 ULN after treatment.

• Abnormal kidney function: Creatinine clearance < 30 ml/min

• Heart failure (NYHA class III or IV)

• Poorly controlled diabetes, characterized by fasting blood glucose > 8.8mmol/L or post-meal blood glucose > 11.1mmol/L after therapy with insulin or oral hypoglycemic agents

• History of congestive heart failure, unstable angina pectoris, myocardial infarction, arterial or venous thrombosis

• Pregnant or breast-feeding patients

• Had a history of any psychiatric diseases, cerebrovascular disease or cognitive sequelae of head injury.

• Participation in another clinical trial within 4 weeks before the start of this trial

• Have an allergy to Daratumumab or any other part of this medicine.

• Previously treated with Daratumumab

• Previously treated with ATG/ALG within 4 months before the start of this trial

• Previously treated with the anti-CD20 monoclonal antibody within 2 months before the start of this trial

• Currently treated with TPO-RA except for a minimum of 4 weeks for washout before the start of this trial

• Patients considered to be ineligible for the study by the investigator for reasons other than above