Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

Sponsor

Bing Han (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05399732

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aplastic Anemia	Drug: Luspatercept	Phase 2

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 ciclosporin versus ciclosporin monotherapy in patients with newly diagnosed transfusion independent NSAA.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Ciclosporin soft capsules（25mg） are produced by North China pharmaceutical Group CorporationCiclosporin soft capsules（25mg） are produced by North China pharmaceutical Group Corporation

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: efficiency and safety in luspatercept plus ciclosporin luspatercept is at a dose of 1.0 mg per kilogram of body weight, administered subcutaneously every 3 weeks，and ciclosporin is at a dose of 3~5mg/kg /day for at least 6 months.	Drug: Luspatercept 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. Other Names: ciclosporin
Active Comparator: controll group in ciclosporin alone ciclosporin is at a dose of 3~5mg/kg /day for at least 6 months.	Drug: Luspatercept 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. Other Names: ciclosporin

Arm

Intervention/Treatment

Experimental: efficiency and safety in luspatercept plus ciclosporin

luspatercept is at a dose of 1.0 mg per kilogram of body weight, administered subcutaneously every 3 weeks，and ciclosporin is at a dose of 3~5mg/kg /day for at least 6 months.

Drug: Luspatercept

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.

Other Names:

ciclosporin

Active Comparator: controll group in ciclosporin alone

ciclosporin is at a dose of 3~5mg/kg /day for at least 6 months.

Drug: Luspatercept

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.

Other Names:

ciclosporin

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age≥18 year-old;
hemoglobin level between 60g/L~10 g/dL;
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;
with normal baseline liver and kidney function;
with no active infection; are not pregnant or nursing;
agree to sign consent forms;
Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Exclusion Criteria:

Congenital aplastic anemia;
Presence of chromosomal aberration;
Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics;
Presence with PNH clone ≥50%;
Patients received HSCT before;
Uncontrolled infection or bleeding with standard treatment;
Allergic to luspatercept CsA or accessories;
HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension;
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;
Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin;
Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants;
Pregnant or nursing (lactating) woman;
Have attended other clinical trials within 3 months