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Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

Primary Purpose

Aplastic Anemia

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Luspatercept

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring NSAA, luspatercept, ORR, non-transfusion dependent

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Peking union medical college hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

efficiency and safety in luspatercept plus ciclosporin

controll group in ciclosporin alone

Arm Description

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.

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

Outcomes

Primary Outcome Measures

overall response rate (ORR)

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)

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

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

Predictors analyses will evaluate the relationship between the effect of these two treatments with molecular mutations PIGA and BCOR and BCORL1 and EPO level.

Full Information

NCT ID

NCT05399732

First Posted

May 24, 2022

Last Updated

May 30, 2022

Sponsor

Bing Han

1. Study Identification

Unique Protocol Identification Number

NCT05399732

Brief Title

Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

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).

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

July 2022 (Anticipated)

Primary Completion Date

January 2023 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Bing Han

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Aplastic Anemia

Keywords

NSAA, luspatercept, ORR, non-transfusion dependent

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

None (Open Label)

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

efficiency and safety in luspatercept plus ciclosporin

Arm Type

Experimental

Arm Description

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.

Arm Title

controll group in ciclosporin alone

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Luspatercept

Other Intervention Name(s)

ciclosporin

Intervention Description

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.

Primary Outcome Measure Information:

Title

overall response rate (ORR)

Description

Time Frame

6 month

Secondary Outcome Measure Information:

Title

Hematologic response-erythroid（HR-E)

Description

HR is defined as a hemoglobin increase from baseline of ≥1.5 g/dL for ≥2 weeks (in the absence of RBC transfusions

Time Frame

6 month

Title

side effects

Description

Time Frame

1 year

Title

predictive factors

Description

Predictors analyses will evaluate the relationship between the effect of these two treatments with molecular mutations PIGA and BCOR and BCORL1 and EPO level.

Time Frame

6 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

Peking union medical college hospital

City

Beijing

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

individual participant data would be accepted upon request

IPD Sharing Time Frame

10years

IPD Sharing Access Criteria

email request

Citations:

PubMed Identifier

15382271

Citation

Howard SC, Naidu PE, Hu XJ, Jeng MR, Rodriguez-Galindo C, Rieman MD, Wang WC. Natural history of moderate aplastic anemia in children. Pediatr Blood Cancer. 2004 Oct;43(5):545-51. doi: 10.1002/pbc.20131.

Results Reference

background

PubMed Identifier

32942816

Citation

Zhang ML, Chen WS, Han B. [Evaluation of the efficacy of cyclosporin A combined with recombined human thrombopoietin for treating patients with non-severe aplastic anemia]. Zhonghua Xue Ye Xue Za Zhi. 2020 Aug 14;41(8):637-642. doi: 10.3760/cma.j.issn.0253-2727.2020.08.004. Chinese.

Results Reference

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PubMed Identifier

34728034

Citation

Chen WS, Zhang ML, Han B. [Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2021 Oct;43(5):736-742. doi: 10.3881/j.issn.1000-503X.13201. Chinese.

Results Reference

background

PubMed Identifier

32619069

Citation

Furlong E, Carter T. Aplastic anaemia: Current concepts in diagnosis and management. J Paediatr Child Health. 2020 Jul;56(7):1023-1028. doi: 10.1111/jpc.14996. Epub 2020 Jul 3.

Results Reference

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PubMed Identifier

25578417

Citation

Desmond R, Townsley DM, Dunbar C, Young NS. Eltrombopag in aplastic anemia. Semin Hematol. 2015 Jan;52(1):31-7. doi: 10.1053/j.seminhematol.2014.10.002. Epub 2014 Oct 31.

Results Reference

background

PubMed Identifier

30146592

Citation

Matsuda K, Koya J, Arai S, Nakazaki K, Nakamura F, Kurokawa M. Cyclosporine Therapy in Patients with Transfusion-independent Non-severe Aplastic Anemia: A Retrospective Analysis. Intern Med. 2019 Feb 1;58(3):355-360. doi: 10.2169/internalmedicine.1372-18. Epub 2018 Aug 24.

Results Reference

background

PubMed Identifier

33747425

Citation

Drexler B, Passweg J. Current evidence and the emerging role of eltrombopag in severe aplastic anemia. Ther Adv Hematol. 2021 Mar 3;12:2040620721998126. doi: 10.1177/2040620721998126. eCollection 2021.

Results Reference

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Efficacy and Safety in Transfusion Independent Non-severe Aplastic Anemia

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