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

Not Applicable

Recruiting

• Conditions: Severe Aplastic Anemia
• Interventions: Drug: Avatrombopag

• Registration Number: NCT05433922
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Study Timeline

• Status Verified: 2022-06
• Study Start: 2022-06-01
• Study First Submitted: 2022-06-11
• Study First Submitted QC: 2022-06-22
• Last Update Submitted: 2022-06-22
• Study First Posted: 2022-06-27
• Last Update Posted: 2022-06-27
• Primary Completion: 2023-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CSA + Avatrombopag	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.

Primary Outcome Measures

Name	Time	Method
OR rate at 24 weeks of treatment	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	24 weeks of treatment	Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation at 24 weeks	24 weeks of treatment	% of patients with transformation to PNH or MDS,AML, or other disease

Secondary Outcome Measures

Name	Time	Method
OR rate and CR rate at 12 weeks	12 weeks of treatment	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	12 weeks of treatment	Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation at 12 weeks	12 weeks of treatment	% of patients with transformation to PNH or MDS,AML, or other disease at 12 weeks

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China