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.

Study Overview

• Status: Completed
• Conditions: Aplastic Anemia; Platelet Transfusion Refractoriness
• Intervention / Treatment: Drug: Daratumumab

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Regenerative Medicine Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Daratumumab	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with platelet transfusion responsiveness	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.	12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to the platelet increment	12 weeks

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2023
• Primary Completion (Actual): October 12, 2024
• Study Completion (Actual): December 1, 2024

Study Registration Dates

• First Submitted: April 3, 2023
• First Submitted That Met QC Criteria: April 25, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Daratumumab; Platelet transfusion refractoriness
• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Anemia, Aplastic; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: IIT2023015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No