Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

A Randomized, Case Controlled Clinical Trial Evaluating the Efficiency and Safety of Luspatercept Plus Cyclosporine Versus Cyclosporine in Newly Diagnosed Transfusion Independent Non-severe Aplastic Anemia (NSAA).

Aplastic anemia (AA) is a rare bone marrow failure disease characterized by bone marrow hypocellularity and peripheral blood pancytopenia. AA is divided into severe AA (SAA) and non-severe AA (NSAA) based on the degree of cytopenia. The first line therapy for SAA or transfusion dependent NSAA is either immunosuppression therapy (IST) or hematopoietic stem cell transplantation (HSCT). Little attention has been paid to patients with anemia but not transfusion dependent, whose quality of life is significantly impaired due to the anemia and other complications.

Recombined human erythropoietin (rhEPO) has been shown to increase the erythroid response and response rate when combined with IST for patients with newly diagnosed AA, either SAA or NSAA. Different from rhEPO, luspatercept is a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands and enhances late-stage erythropoiesis, and has been shown the promising efficiency in the erythropoiesis in patients with lower risk myelodysplastic syndrome (MDS) in the phase II and III clinical trials. This randomized control study aimed to compare the 6-month efficacy and safety of the combination of luspatercept and cyclosporine versus cyclosporine monotherapy in patients with newly diagnosed transfusion independent NSAA.

Inclusion Criteria:

1. age≥18 year-old;
2. hemoglobin level between 60g/L~10 g/dL;
3. newly diagnosed patients have at least one of the followings: #absolute neutrophil count <1.5×109/L, #platelet count < 30×109/L, # hemoglobin level < 100g/L;
4. with normal baseline liver and kidney function;
5. with no active infection; are not pregnant or nursing;
6. agree to sign consent forms;
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

1. Congenital aplastic anemia;
2. Presence of chromosomal aberration;
3. Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics;
4. Presence with PNH clone ≥50%;
5. Patients received HSCT before;
6. Uncontrolled infection or bleeding with standard treatment;
7. Allergic to luspatercept CsA or accessories;
8. HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension;
9. Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site, unstable angina pectoris, uncontrolled hypertension(>180/100mmHg)#pulmonary artery hypertension;
10. Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin;
11. Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
12. Pregnant or nursing (lactating) woman;
13. Have attended other clinical trials within 3 months