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Efficacy and Safety of CSA and Avatrombopag for the Treatment of SAA in the Elderly (SAA)

Primary Purpose

Severe Aplastic Anemia

Status

Recruiting

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

Avatrombopag

About this trial

This is an interventional treatment trial for Severe Aplastic Anemia focused on measuring Avatrombopag, Aplastic Anemia, elderly, sever

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

elderly patients with V/SAA with a definite diagnosis.
age greater than 60 years, male or female.
Subjects must complete all screening assessments as outlined in the trial protocol.
Able to swallow or administer the drug orally.
Cannot tolerate or refuse ATG therapy.
No prior treatment with cyclosporine, tacrolimus or hormones or treatment for no more than 2 weeks.
No prior application of TPO receptor agonists (including Thrombopoietin, Eltrombopag, Hetrombopag, etc.) or application of TPO receptor agonists for treatment with ≤ 5 total doses and ≤ 7 days of TPO receptor agonist drugs such as Eltrombopag, Hetrombopag, etc.
Informed consent must be signed prior to the start of all specific study procedures, in consideration of the patient's condition, or by a member of the patient's immediate family if the patient's signature is not conducive to the treatment of the condition.

Exclusion Criteria:

No subject shall be enrolled in this study if he/she meets any of the following criteria.

known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of allogeneic cytopenias and bone marrow hypoproliferative disorders (e.g. hemolytic PNH, hypoproliferative MDS/AML, autoantibody-mediated allogeneic cytopenias, etc.);
Patients with uncontrolled bleeding and/or infection despite standard treatment.
patients with previous history of hematopoietic stem cell transplantation;
previous history of thrombosis.
Patients with concurrent malignancy or potential cancer on immunosuppressive therapy.
Those who are considered unsuitable for enrollment by the investigator.

Sites / Locations

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CSA + Avatrombopag

Arm Description

cyclosporine 3 mg/kg orally in two doses, with cyclosporine trough concentrations maintained at 200-250 ng/ml for 3 months to achieve maximum efficacy and then tapered by 25 mg every 3 months; Avatrombopag: two dosing groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks.If the 40 mg dose group trial meets the desired trial objectives, the 60 mg dose group trial will not be conducted.

Outcomes

Primary Outcome Measures

OR rate at 24 weeks of treatment

Percentage of the total number of patients receiving treatment who received a response at 24 weeks of treatment

Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 24 weeks of treatment

Incidence of Treatment-Emergent AE by CTCAE

Percentage of patients with transformation at 24 weeks

% of patients with transformation to PNH or MDS,AML, or other disease

Secondary Outcome Measures

OR rate and CR rate at 12 weeks

Percentage of patients who received a response and who receive a complete response at 12 weeks of treatment

Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks

Incidence of Treatment-Emergent AE by CTCAE

Percentage of patients with transformation at 12 weeks

% of patients with transformation to PNH or MDS,AML, or other disease at 12 weeks

Full Information

NCT ID

NCT05433922

First Posted

June 11, 2022

Last Updated

June 22, 2022

Sponsor

Institute of Hematology & Blood Diseases Hospital, China

1. Study Identification

Unique Protocol Identification Number

NCT05433922

Brief Title

Efficacy and Safety of CSA and Avatrombopag for the Treatment of SAA in the Elderly

Acronym

SAA

Official Title

A Multicenter, Single-arm Clinical Study of the Efficacy and Safety of CSA in Combination With Avatrombopag for the Treatment of Primary Treatment of Severe Aplastic Anemia in the Elderly

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 1, 2022 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Institute of Hematology & Blood Diseases Hospital, China

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a multicenter, single-arm clinical study. The objective was to evaluate the efficacy and safety of CSA in combination with Avatrombopag in elderly patients with very/sever aplastic anemia treated for the first time. The design was: cyclosporine 3 mg/kg orally in two divided doses, with cyclosporine trough concentrations maintained at 200-250 ng/ml for 3 months to achieve maximum efficacy, and Avatrombopag, which was administered in two dose groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks. Forty patients are expected to be enrolled in each dose group, and a total of 80 patients are expected to be enrolled if both dose groups are conducted. Evaluation endpoint: OR rate at 24 weeks of treatment.

Detailed Description

This is a multicenter, single-arm clinical study to evaluate the efficacy and safety of CSA combined with Avatrombopag. The patients are older than 60 years with diagnosis of very sever/sever aplastic anemia(V/SAA) without treatment before. CSA is started at 3 mg/kg orally in two doses. Concentrations maintained at 200-250 ng/ml to achieve maximum efficacy and then tapered by 25 mg every 3 months; Avatrombopag: two dosing groups, 40 mg orally once daily and 60 mg orally once daily, for a total of 24 weeks；Each dose group is expected to include 40 patients each. If the 40 mg dose group trial meets the desired trial objectives, the 60 mg dose group trial will not be conducted, and if the 40 mg dose group does not meet the desired trial objectives, the 60 mg dose group trial will be continued. A total of 80 patients were expected to be included if both dose groups were conducted.Overall response rate at 24 weeks of treatment and adverse events are the evaluation endpoint.Secondary study endpoints were: CRR and ORR at 12 and 52 weeks of treatment, CRR at 24 weeks, survival, and clonal evolution in follow-up.

6. Conditions and Keywords

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

Severe Aplastic Anemia

Keywords

Avatrombopag, Aplastic Anemia, elderly, sever

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

CSA + Avatrombopag

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Avatrombopag

Other Intervention Name(s)

CSA

Intervention Description

cyclosporine in combination with Avatrombopag to treat

Primary Outcome Measure Information:

Title

OR rate at 24 weeks of treatment

Description

Percentage of the total number of patients receiving treatment who received a response at 24 weeks of treatment

Time Frame

24 weeks of treatment

Title

Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 24 weeks of treatment

Description

Incidence of Treatment-Emergent AE by CTCAE

Time Frame

24 weeks of treatment

Title

Percentage of patients with transformation at 24 weeks

Description

% of patients with transformation to PNH or MDS,AML, or other disease

Time Frame

24 weeks of treatment

Secondary Outcome Measure Information:

Title

OR rate and CR rate at 12 weeks

Description

Percentage of patients who received a response and who receive a complete response at 12 weeks of treatment

Time Frame

12 weeks of treatment

Title

Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 12 weeks

Description

Incidence of Treatment-Emergent AE by CTCAE

Time Frame

12 weeks of treatment

Title

Percentage of patients with transformation at 12 weeks

Description

% of patients with transformation to PNH or MDS,AML, or other disease at 12 weeks

Time Frame

12 weeks of treatment

Other Pre-specified Outcome Measures:

Title

OR rate and CR rate at 52 weeks

Description

Percentage of patients who received a response and who receive a complete response at 52 weeks of treatment

Time Frame

52 weeks of treatment

Title

Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 52 weeks

Description

Incidence of Treatment-Emergent AE by CTCAE

Time Frame

52 weeks of treatment

Title

Percentage of patients with transformation at 52 weeks

Description

% of patients with transformation to PNH or MDS,AML, or other disease at 52 weeks

Time Frame

52 weeks of treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: elderly patients with V/SAA with a definite diagnosis. age greater than 60 years, male or female. Subjects must complete all screening assessments as outlined in the trial protocol. Able to swallow or administer the drug orally. Cannot tolerate or refuse ATG therapy. No prior treatment with cyclosporine, tacrolimus or hormones or treatment for no more than 2 weeks. No prior application of TPO receptor agonists (including Thrombopoietin, Eltrombopag, Hetrombopag, etc.) or application of TPO receptor agonists for treatment with ≤ 5 total doses and ≤ 7 days of TPO receptor agonist drugs such as Eltrombopag, Hetrombopag, etc. Informed consent must be signed prior to the start of all specific study procedures, in consideration of the patient's condition, or by a member of the patient's immediate family if the patient's signature is not conducive to the treatment of the condition. Exclusion Criteria: No subject shall be enrolled in this study if he/she meets any of the following criteria. known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of allogeneic cytopenias and bone marrow hypoproliferative disorders (e.g. hemolytic PNH, hypoproliferative MDS/AML, autoantibody-mediated allogeneic cytopenias, etc.); Patients with uncontrolled bleeding and/or infection despite standard treatment. patients with previous history of hematopoietic stem cell transplantation; previous history of thrombosis. Patients with concurrent malignancy or potential cancer on immunosuppressive therapy. Those who are considered unsuitable for enrollment by the investigator.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fengkui Zhang, doctor

Phone

8602223909229

fkzhang@ihcams.ac.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Li Zhang, doctor

Phone

8602223909223

zhangli@ihcams.ac.cn

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Li Zhang, doctor

Organizational Affiliation

Anemia Treatment Center

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Lei Ye, doctor

Organizational Affiliation

Anemia Treatment Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

City

Tianjin

State/Province

Tianjin

ZIP/Postal Code

300020

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fengkui Zhang, doctor

Phone

8602223909229

fkzhang@ihcams.ac.cn

First Name & Middle Initial & Last Name & Degree

Li Zhang, doctor

Phone

8602223909223

zhangli@ihcams.ac.cn

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

You can ask for the researcher after completing the experiment

IPD Sharing Time Frame

Follow-up and publication of the paper are planned for December 2024

IPD Sharing Access Criteria

After the paper is written and published

Citations:

PubMed Identifier

18379007

Citation

Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008 Apr;93(4):489-92. doi: 10.3324/haematol.12855. No abstract available.

Results Reference

result

PubMed Identifier

28219216

Citation

Red Blood Cell Disease (Anemia) Group, Chinese Society of Hematology, Chinese Medical Association. [Chinese expert consensus on the diagnosis and treatment of aplastic anemia (2017)]. Zhonghua Xue Ye Xue Za Zhi. 2017 Jan 14;38(1):1-5. doi: 10.3760/cma.j.issn.0253-2727.2017.01.001. No abstract available. Chinese.

Results Reference

result

PubMed Identifier

30262561

Citation

Contejean A, Resche-Rigon M, Tamburini J, Alcantara M, Jardin F, Lengline E, Ades L, Bouscary D, Marcais A, Lebon D, Chabrot C, Terriou L, Barraco F, Banos A, Bussot L, Cahn JY, Hirsch P, Maillard N, Simon L, Fornecker LM, Socie G, de Latour RP, de Fontbrune FS. Aplastic anemia in the elderly: a nationwide survey on behalf of the French Reference Center for Aplastic Anemia. Haematologica. 2019 Feb;104(2):256-262. doi: 10.3324/haematol.2018.198440. Epub 2018 Sep 27.

Results Reference

result

PubMed Identifier

30504345

Citation

Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):450-456. doi: 10.1182/asheducation-2018.1.450.

Results Reference

result

PubMed Identifier

28423296

Citation

Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.

Results Reference

result

Learn more about this trial

Efficacy and Safety of CSA and Avatrombopag for the Treatment of SAA in the Elderly

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