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

NCT05433922 | Unknown

• 1 other identifier: fkzhang
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Severe Aplastic Anemia

Keywords

Avatrombopag; Aplastic Anemia; elderly; sever

Outcome Measures

Primary Outcomes (3)

• 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

  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

  24 weeks of treatment

• Percentage of patients with transformation at 24 weeks

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

  24 weeks of treatment

Secondary Outcomes (3)

• OR rate and CR rate at 12 weeks

  12 weeks of treatment

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

  12 weeks of treatment

• Percentage of patients with transformation at 12 weeks

  12 weeks of treatment

Other Outcomes (3)

• OR rate and CR rate at 52 weeks

  52 weeks of treatment

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

  52 weeks of treatment

• Percentage of patients with transformation at 52 weeks

  52 weeks of treatment

Study Arms (1)

CSA + Avatrombopag

EXPERIMENTAL

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.

Drug: Avatrombopag

Interventions

Avatrombopag DRUG

cyclosporine in combination with Avatrombopag to treat

Also known as: CSA

CSA + Avatrombopag

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

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

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (5)

• 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.

  PMID: 18379007 RESULT

• 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.

  PMID: 28219216 RESULT

• 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.

  PMID: 30262561 RESULT

• 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.

  PMID: 30504345 RESULT

• 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.

  PMID: 28423296 RESULT

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Li Zhang, doctor

  Anemia Treatment Center

  STUDY DIRECTOR

• Lei Ye, doctor

  Anemia Treatment Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fengkui Zhang, doctor

CONTACT

8602223909229; fkzhang@ihcams.ac.cn

Li Zhang, doctor

CONTACT

8602223909223; zhangli@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Anemia Treatment Center

Study Record Dates

• First Submitted: June 11, 2022
• First Posted: June 27, 2022
• Study Start: June 1, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: June 27, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Follow-up and publication of the paper are planned for December 2024
• Access Criteria: After the paper is written and published

Locations

CN (1)