Efficacy and Safety of CsA+AVA in the Treatment of NSAA in the Elderly

Phase 2

Recruiting

Brief Summary: For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag (AVA), which has a slight adverse reaction, can theoretically improve the hematological response rate in elderly patients with non-severe aplastic anemia (NSAA) without significantly increasing adverse reactions. Based on this, this study treated NS...

Detailed Description: Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according to the severity of the disease. Anti-thymocyte globulin (ATG) in combination with CsA is the most typical combined immunosuppressive therapy regimen. For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag, which...

Recruitment & Eligibility

Inclusion Criteria

Elderly patients with well-defined NSAA anemia who meet the diagnostic criteria for aplastic anemia (AA) but do not meet the diagnostic criteria for severe aplastic anemia (SAA).
Age 60 years or older, male or female.
Able to swallow or administer orally.
Intolerant or refused anti-thymocyte globulin treatment
No previous treatment with cyclosporine, tacrolimus or hormones or treatment for less than 1 month.
No prior treatment with thrombopoietin (TPO) receptor agonists (including eltrombopag, herombopag, romiplostim, etc.) 8. Informed consent must be signed before the start of all specific research procedures. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the disease, the informed consent shall be signed by the patient's immediate family.

Exclusion Criteria

Known congenital AA (such as Fanconi anemia) and other causes of pancytopenia and hematological bone marrow disorders;
With paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50%
With a history of hematopoietic stem cell transplantation.
History of thrombosis
Patients with underlying cancer who also have malignant tumors or are receiving immunosuppressive therapy.
Baseline creatine levels greater than twice of the upper limit of normal (ULN) and/or alanine aminotransferase (ALT) greater than 2.5 times of the ULN;
Serious heart, liver and kidney disease.
With uncontrolled bleeding and/or infection after standard treatment.
Participants considered unsuitable for inclusion by the researchers.

Arm && Interventions

Group	Intervention	Description
treatment group	Avatrombopag	Cyclosporine: 3mg/kg/d 3-5mg/kg bid was administered to maintain the trough concentration at 100-200 μg/ml; Avatrombopag: The dosage was 40\~60mg orally, once a day, and the dosage was adjusted according to the subject's platelet count. The drug was administered for 24 weeks (6 months).
treatment group	Ciclosporin	Cyclosporine: 3mg/kg/d 3-5mg/kg bid was administered to maintain the trough concentration at 100-200 μg/ml; Avatrombopag: The dosage was 40\~60mg orally, once a day, and the dosage was adjusted according to the subject's platelet count. The drug was administered for 24 weeks (6 months).

Primary Outcome Measures

Name	Time	Method
ORR at 6 Months	6 months	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR)

Secondary Outcome Measures

Name	Time	Method
Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia	12 months	Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline \< 10% that rose to greater than 50%...
Relapse rate	6 months, last follow-up	Relapse was defined as a substantial or progressive decline in at least one blood lineage counts of the responders that required the reinitiation or augmentation of AVA.
ORR at 1, 2, 3 Months and at the end of follow-up	1, 2, 3 Months, last follow-up	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR)
Changes in Platelet in the Absence of Platelet Transfusion	6 months	The change in hematology values (platelet) were evaluated
Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion	6 months	The change in hematology values ( haemoglobin) were evaluated