Clinical trial NCT06964971: Treatment of Transfusion-dependent Nonsevere Aplastic Anemia With Luspatercept: a Multicenter Prospective Clinical Study
Official title: Treatment of Transfusion-dependent Nonsevere Aplastic Anemia With Luspatercept: a Multicenter Prospective Clinical Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Transfusion-dependent Non-severe Aplastic Anemia
Lead sponsor: The First Affiliated Hospital of Zhejiang Chinese Medical University
Sponsor class: OTHER
First posted: 2025-05-11
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Control Group: Patients will continue with their original basic treatment regimen for the disease (immunosuppressants, androgens（either alone or in combination）) under observation.

Treatment Group: In addition to the original basic treatment for the disease, patients will be further divided based on whether iron chelation therapy is used, into two subgroups: Luspatercept monotherapy group and Luspatercept combined with deferasirox group.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Hemoglobin
timeFrame: 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 outcomes:
measure: platelets
timeFrame: 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).
measure: Ferritin
timeFrame: Baseline (30 days before treatment), treatment phase: 12 weeks ( once every 3 weeks ), mid-treatment phase: 12 weeks (once every 3 weeks)
measure: Proportion of patients transfusion-free for ≥8 weeks and ≥12 weeks
timeFrame: 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)
measure: Overall response rate (ORR; CR + PR) at Week 12 and Week 24 of treatment
timeFrame: Week 12 and Week 24
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang Chinese Medical University
state: Zhejiang
Study officials:
References: