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

Обзор

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.

Вмешательства

• Препарат 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).
• Препарат 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.

Первичные конечные точки

• Hemoglobin [Срок оценки: 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).]

Вторичные конечные точки (4)

• platelets [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Week 12 and Week 24]

Критерии участия

Критерии включения

• 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:

• The patient has not received and does not consider HSCT or ATG treatment for at least the next six months;
• If maintaining oral immunosuppressive therapy, the course must be at least 6 months and assessed as ineffective;
• If maintaining androgen therapy, the course must be at least 3 months and assessed as ineffective;
• If maintaining recombinant human erythropoietin therapy, the course must be at least 3 months and assessed as ineffective;
• 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;
• 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.

Критерии исключения

• 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).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Affiliated Hospital of Zhejiang Chinese Medical University — Ханчжоу

Идентификаторы

NCT: NCT06964971 · 2025-KLS-046-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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