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

NCT ID: NCT05433922

Last Updated: 2022-06-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2024-12-31

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.

Conditions

Severe Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CSA + Avatrombopag

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.

Group Type: EXPERIMENTAL

Avatrombopag

Intervention Type: DRUG

cyclosporine in combination with Avatrombopag to treat

Interventions

Avatrombopag

cyclosporine in combination with Avatrombopag to treat

Intervention Type: DRUG

Other Intervention Names

CSA

Eligibility Criteria

Inclusion Criteria

1. elderly patients with V/SAA with a definite diagnosis.

2. age greater than 60 years, male or female.

3. Subjects must complete all screening assessments as outlined in the trial protocol.

4. Able to swallow or administer the drug orally.

5. Cannot tolerate or refuse ATG therapy.

6. No prior treatment with cyclosporine, tacrolimus or hormones or treatment for no more than 2 weeks.

7. 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.

8. 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.

1. 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.);

2. Patients with uncontrolled bleeding and/or infection despite standard treatment.

3. patients with previous history of hematopoietic stem cell transplantation;

4. previous history of thrombosis.

5. Patients with concurrent malignancy or potential cancer on immunosuppressive therapy.

6. Those who are considered unsuitable for enrollment by the investigator.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Fengkui Zhang

Director of Anemia Treatment Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Li Zhang, doctor

Role: STUDY_DIRECTOR

Anemia Treatment Center

Lei Ye, doctor

Role: PRINCIPAL_INVESTIGATOR

Anemia Treatment Center

Locations

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

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fengkui Zhang, doctor

Role: CONTACT

fkzhang@ihcams.ac.cn

8602223909229

Li Zhang, doctor

Role: CONTACT

zhangli@ihcams.ac.cn

8602223909223

Facility Contacts

Fengkui Zhang, doctor

Role: primary

fkzhang@ihcams.ac.cn

8602223909229

Li Zhang, doctor

Role: backup

zhangli@ihcams.ac.cn

8602223909223

References

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.

Reference Type: RESULT

PMID: 18379007 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28219216 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30262561 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30504345 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28423296 (View on PubMed)

Other Identifiers

fkzhang

Identifier Type: -

Identifier Source: org_study_id