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

Severe Aplastic Anemia Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05433922
• Other study ID #: fkzhang
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: June 2022
• Source: Institute of Hematology & Blood Diseases Hospital
• Contact: Fengkui Zhang, doctor
• Phone: 8602223909229
• Email: fkzhang[@]ihcams.ac.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Severe Aplastic Anemia

Intervention

Drug:
• Avatrombopag
cyclosporine in combination with Avatrombopag to treat

Locations

Country	Name	City	State
China	Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Hematology & Blood Diseases Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Contejean A, Resche-Rigon M, Tamburini J, Alcantara M, Jardin F, Lengliné E, Adès L, Bouscary D, Marçais A, Lebon D, Chabrot C, Terriou L, Barraco F, Banos A, Bussot L, Cahn JY, Hirsch P, Maillard N, Simon L, Fornecker LM, Socié G, de Latour RP, de Fontbr — View 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.i — View 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. Review. — View 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 An — View Citation

Young NS, Kaufman DW. The epidemiology of acquired aplastic anemia. Haematologica. 2008 Apr;93(4):489-92. doi: 10.3324/haematol.12855. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	OR rate and CR rate at 52 weeks	Percentage of patients who received a response and who receive a complete response at 52 weeks of treatment	52 weeks of treatment
Other	Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading at 52 weeks	Incidence of Treatment-Emergent AE by CTCAE	52 weeks of treatment
Other	Percentage of patients with transformation at 52 weeks	% of patients with transformation to PNH or MDS,AML, or other disease at 52 weeks	52 weeks of treatment
Primary	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
Primary	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
Primary	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	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	12 weeks of treatment
Secondary	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	12 weeks of treatment
Secondary	Percentage of patients with transformation at 12 weeks	% of patients with transformation to PNH or MDS,AML, or other disease at 12 weeks	12 weeks of treatment