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

NCT ID: NCT05832216

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-17
• Study Completion Date: 2024-12-01

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.

Conditions

Aplastic Anemia; Platelet Transfusion Refractoriness

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Daratumumab

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

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.

Interventions

Daratumumab

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Regenerative Medicine Center

Tianjin, Tianjin Municipality, China

Countries

China

References

Gao Z, Pan H, Zhang L, Li W, Li R, Zhao J, Luo Y, Lian Y, Yu X, Kuang Z, Nie N, Li J, Huang J, Zhao X, Li Y, Fang L, Ge M, Zheng Y, Shi J. Targeting CD38 with daratumumab for platelet transfusion refractoriness in aplastic anemia. Blood. 2025 Jun 26;145(26):3189-3193. doi: 10.1182/blood.2025029006.

Reference Type: DERIVED

PMID: 40331918 (View on PubMed)

Other Identifiers

IIT2023015

Identifier Type: -

Identifier Source: org_study_id