Aplastic Anemia
Conditions
Keywords
NSAA, luspatercept, ORR, non-transfusion dependent
Brief summary
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.
Detailed description
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.
Interventions
DRUGLuspatercept
Patients in each group will be treated for at least 6 months and continue the treatment for an additional 6 months unless disease progress or have intolerable side effects.
DRUGCyclosporine
Cyclosporine was administered at a 3-5 mg/(kd/d) and maintained at a 100-200 ng/ml trough plasma concentration.
Sponsors
Bristol-Myers Squibb
Bing Han
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Cyclosporine soft capsules（25mg） are produced by North China pharmaceutical Group Corporation
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate (ORR) | 6 month | Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR); HR defined as a hemoglobin increase from baseline of ≥1.5 g/dL for ≥2 weeks (in the absence of RBC transfusions) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic response-erythroid（HR-E) | 6 month | HR is defined as a hemoglobin increase from baseline of ≥1.5 g/dL for ≥2 weeks (in the absence of RBC transfusions |
| side effects | 1 year | Safety analyses include assessments of the incidence and severity of adverse events; all adverse events that occurred or worsened during the treatment period will be reported, as well as adverse events that occurred later but are considered by the investigator to be related to the trial drug. |
| predictive factors | 6 month | Predictors analyses will evaluate the relationship between the effect of these two treatments with molecular mutations PIGA and BCOR and BCORL1 and EPO level. |
Countries
China
Outcome results
None listed