Clinical trial NCT06424639: Luspatercept Plus CsA vs CsA for the Treatment of Newly Diagnosed Non-Transfusion-Dependent NSAA
Official title: A Randomized, Controlled Trial Comparing the Safety and Efficacy of Luspatercept Plus Cyclosporine Versus Cyclosporine Alone for the Treatment of Newly Diagnosed Non-transfusion-dependent Non-severe Aplastic Anemia (NSAA)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Aplastic Anemia
Keywords: Aplastic Anemia
Luspatercept
CsA
randomized controlled study
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2024-05-22
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In a randomized, controlled clinical trial, the efficacy and safety of rodsipil combined with cyclosporine versus cyclosporine alone in the treatment of newly diagnosed non-transfusion-dependent NSAA were compared.

Detailed description: Conduct a comparative evaluation of the effectiveness and safety of Luspatercept combined with cyclosporine versus cyclosporine monotherapy in the treatment of newly diagnosed non-transfusion-dependent non-severe aplastic anemia (NSAA). Patients were randomized in a 1:1 ratio and assigned to one of two groups: Group A, Luspatercept combined with cyclosporine: received Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), cyclosporine (3-5mg/kg/day), adjusted based on hematological parameters, for at least 6 months to assess efficacy. Effective patients continued to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage; Group B, cyclosporine: received 3-5mg/kg/day, adjusted based on hematological parameters, for at least 6 months to assess efficacy, with effective patients continuing to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage. Hgb below 60g/L was allowed, or in emergency conditions, blood transfusion was allowed. Platelets below 20×10\^9/L or with obvious bleeding tendency were allowed to receive platelet transfusion. If neutrophil count was below 1.0×10\^9/L, G-CSF was allowed until neutrophil count recovered to above 1.0×10\^9/L. Symptoms, treatment-related adverse events, signs, blood transfusion volume, and laboratory tests (including reticulocyte count) were recorded at least every 3 months for the first 3 months, and every 6 months thereafter until 6 months, and bone marrow aspiration, biopsy, and chromosome examination were performed at least every 6 months to observe efficacy and safety.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. Hemoglobin level of 6-10 g/dL
3. Definition of NSAA: Patients with AA diagnosis but not SAA or VSAA diagnosis (at least two of the following conditions can be diagnosed as AA: (i) Hemoglobin \< 100 g/L; (ii) Platelet count \< 50×10\^9/L; (iii) Neutrophil count \< 1.5×10\^9/L. SAA diagnosis criteria include less than 25% (or 25-50%, but residual hematopoietic cells \< 30%) of bone marrow cells, plus at least two of the following conditions: (i) Neutrophil count \< 0.5×10\^9/L; (ii) Platelet count \< 20×10\^9/L; (iii) Retroperitoneal lymph node count \< 20×10\^9/L. VSAA meets the criteria for SAA, but with neutrophil count \< 0.2×10\^9/L. (British guidelines, 2015))
4. No active infection
5. No other concurrent neoplasms (except in situ carcinoma)
6. Baseline liver and renal function within 1.5 times of normal value
7. No pregnancy or breastfeeding
8. Agree to sign informed consent form
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Exclusion Criteria:

1. Congenital aplastic anemia
2. Presence of chromosomal aberrations
3. Cytogenetic evidence of clonal hematological myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML)
4. PNH clone ≥50%
5. Previous use of alemtuzumab, any ATG, or any dose of cyclosporine for immunosuppressive treatment
6. Previous hematopoietic stem cell transplant (HSCT)
7. Uncontrolled infection or bleeding under standard treatment
8. Allergy to rituximab, cyclosporine, or excipients
9. History of allergy to polyethylene glycol (PEG) 80
10. Active infection or cirrhosis of the liver or portal hypertension due to HIV, HCV, or HBV
11. Screening QTcF (Fridericia QT corrected formula) less than 450 milliseconds or less than 480 milliseconds of bundle branch block determined by three ECG averages, and assessed on-site; unstable angina; uncontrolled hypertension (\>180/100 mmHg); pulmonary hypertension
12. Any malignant tumor within 5 years, except local basal cell carcinoma; previous thromboembolic event, history of myocardial infarction or stroke (including antiphospholipid syndrome); currently using anticoagulants
13. Pregnant or lactating women
14. Participated in another clinical trial within 3 months

Primary outcomes:
measure: overall response rate (ORR)
timeFrame: 6 month
Secondary outcomes:
measure: overall response rate (ORR)
timeFrame: 12 month
measure: adverse event rate
timeFrame: 12 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Bing Bing, PhD
role: PRINCIPAL_INVESTIGATOR
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