Treatment of Transfusion-dependent Nonsevere Aplastic Anemia With Luspatercept: a Multicenter Prospective Clinical Study

The goal of this clinical trial is to learn whether Luspatercept alone or in combination with Deferasirox can promote hematopoietic function in patients with transfusion-dependent non-severe aplastic anemia, as well as to assess the safety and efficacy of this treatment approach.

The main questions it aims to answer is:

whether the combination therapy of Luspatercept and Deferasirox can improve hemoglobin levels in these patients.

Participants will receive Luspatercept every 3 to 5 weeks based on hemoglobin response, undergo complete blood counts every 1 to 3 weeks, and receive other necessary evaluations as required.

Study Overview

• Status: Not yet recruiting
• Conditions: Transfusion-dependent Non-severe Aplastic Anemia
• Intervention / Treatment: Drug: Luspatercept; Drug: Luspatercept combine with Deferasirox

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dijiong Wu, Ph.D.; Phone Number: +86 13989463963; Email: wudijiong@zcmu.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang Chinese Medical University
      • Contact: Hangping Ge; Phone Number: +86 13738092542; Email: canthy1216@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Age >= 18 years; 2.According to the "Chinese Guidelines for the Diagnosis and Treatment of Aplastic Anemia (2022 Edition)", the patient must be diagnosed with transfusion-dependent non-severe aplastic anemia (TD-NSAA) and meet the requirement of erythroid hyperplasia in bone marrow aspiration from the posterior iliac crest and/or sternum being more than 15%; 3.If not newly diagnosed with TD-NSAA, and there are combined primary disease maintenance medications, the following conditions must be met:

  1. The patient has not received and does not consider HSCT or ATG treatment for at least the next six months;
  2. If maintaining oral immunosuppressive therapy, the course must be at least 6 months and assessed as ineffective;
  3. If maintaining androgen therapy, the course must be at least 3 months and assessed as ineffective;
  4. If maintaining recombinant human erythropoietin therapy, the course must be at least 3 months and assessed as ineffective;
  5. If maintaining thrombopoietin receptor agonist (TPO-RA) therapy, the duration must be >=6 months with confirmed inefficacy, and a washout period of >=1 month is required before study enrollment;
  6. If the above maintenance medication durations are not met, a washout period of at least 1 month is required; 4.Serum ferritin level >= 1000 ng/ml; 5.Complete whole exome sequencing and MDS/AA next-generation sequencing testing are required.

Exclusion Criteria:

• 1. Severe hepatic dysfunction (ALT or AST ≥ 3 × ULN); 2.Severe renal impairment (eGFR < 30 ml/min/1.73m² or patients with end-stage renal disease); 3.Cardiac disease, including New York Heart Association (NYHA) Class 3 or higher heart failure, or severe arrhythmia requiring treatment, or recent myocardial infarction within 6 months of randomization; 4.Patients with uncontrolled hypertension, with controlled hypertension according to NCI CTCAE version 5.0 considered as ≤ Grade 1 for this protocol; 5.Patients with a PNH clone > 1%; 6.Patients planning to become pregnant or who are pregnant; 7.Surgical or clinical conditions that may significantly alter drug absorption, distribution, metabolism, or excretion (e.g., gastritis, ulcers, history of gastrointestinal or rectal bleeding; history of major gastrointestinal surgery); 8.Patients carrying congenital bone marrow failure-related gene mutations (homozygous or heterozygous, regardless of whether they are pathogenic/benign/likely benign/ of uncertain significance).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group1; basic treatment regimen + Luspatercept alone	Drug: Luspatercept; The recommended starting dose of luspatercept is 1.5 mg/kg administered subcutaneously (SC) once every 3 weeks. Treatment response should be evaluated and dosage adjusted after at least 3 treatment cycles (9 weeks).
Experimental: Treatment Group2; basic treatment regimen + Luspatercept combine with Deferasirox	Drug: Luspatercept combine with Deferasirox; The recommended starting dose of luspatercept is 1.5 mg/kg administered subcutaneously (SC) once every 3 weeks. Treatment response should be evaluated and dosage adjusted after at least 3 treatment cycles (9 weeks). For patient with platelet counts < 50×10⁹/L: Deferasirox dosage: 8-10 mg/kg/day, orally. For platelet counts ≥ 50×10⁹/L: Deferasirox dosage: 20 mg/kg/day, orally. Discontinue deferasirox if serum ferritin drops below 500 μg/L.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin	Mild anemia: Defined as a hemoglobin level <120 g/L in adult males or <110 g/L in adult females, but >90 g/L. Moderate anemia: Hemoglobin level between 60-90 g/L. Severe anemia: Hemoglobin level between 30-60 g/L. Extremely severe anemia: Hemoglobin level <30 g/L.	Baseline (1 month before treatment), treatment phase: 12 weeks (twice weekly in weeks 1 / 2, once weekly in week 3, once every 3 weeks ), mid-treatment phase: 12 weeks (once every 3 weeks), follow-up period: 48 weeks (once every 12 weeks).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
platelets		Baseline (30 days before treatment), treatment phase: 12 weeks (twice weekly in weeks 1 / 2, once weekly in week 3, once every 3 weeks ), mid-treatment phase: 12 weeks (once every 3 weeks).
Ferritin		Baseline (30 days before treatment), treatment phase: 12 weeks ( once every 3 weeks ), mid-treatment phase: 12 weeks (once every 3 weeks)
Proportion of patients transfusion-free for ≥8 weeks and ≥12 weeks		treatment phase: 12 weeks (twice weekly in weeks 1 / 2, once weekly in week 3, once every 3 weeks ), mid-treatment phase: 12 weeks (once every 3 weeks)
Overall response rate (ORR; CR + PR) at Week 12 and Week 24 of treatment	ORR: Overall Response Rate (defined as the proportion of patients achieving complete response [CR] or partial response [PR]).	Week 12 and Week 24

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2025
• Primary Completion (Estimated): May 20, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 7, 2025
• First Submitted That Met QC Criteria: May 7, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Failure Disorders; Hematologic Diseases; Bone Marrow Diseases; Anemia; Anemia, Aplastic; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hematinics; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox; Luspatercept; Immunoglobulin Fc Fragments
• Other Study ID Numbers: 2025-KLS-046-02

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