Aplastic Anemia, Platelet Transfusion Refractoriness
Conditions
Keywords
Platelet transfusion refractoriness, Daratumumab
Brief summary
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.
Interventions
DRUGDaratumumab
Daratumumab is a monoclonal globulin targeting the CD38 molecule of immune cells, which can eliminate antigen-presenting cells such as dendritic cells and macrophages, and indirectly reduce the production of autoantibodies. In addition, Daratumumab reduces autoantibody levels by targeting plasma cells, B lymphocytes and T lymphocytes.
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with platelet transfusion responsiveness | 12 weeks | To evaluate the safety and efficacy of Daratumumab to increase the platelet increment, defined as Corrected Count Increment (CCI) ≥7500/μL at 60 min or CCI≥4500/μL at 24 hrs post transfusion, or platelet transfusion independence, i.e. PLT\>10×10\^9/L without any bleeding events. |
Secondary
| Measure | Time frame |
|---|---|
| Time to the platelet increment | 12 weeks |
Countries
China
Outcome results
None listed