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CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly

Registration Number
NCT05996393
Lead Sponsor
Peking Union Medical College Hospital
Brief Summary

This is a multicenter, prospective, randonmized study. Our previous retrospective study showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag (EPAG) had similar efficacy to CsA+ATG+EPAG. Since the action mechanism of AVA and EPAG is not exactly the same, and the metabolic level of the elderly is not the same as that of younger patients, it is unknown whether there are predictive factors of efficacy in the treatment of AVA. We wondered whether CsA+AVA could achieve an efficacy similar to CsA+ATG+AVA in the Elderly. Meanwhile, to explore the predictive factors of efficacy, to find out a safe and effective treatment strategy for the Elderly.

Detailed Description

Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according to the severity of the disease. For SAA patients with o condition of hematopoietic stem cell transplantation, guideline recommended ciclosporin A (CsA) + anti-thymocyte immunoglobulin (ATG) + thrombopoietin receptor agonists (TPO-RA) as the first-line therapy. Our previous retrospective study showed that for SAA patients who were intolerant to ATG, CsA+ eltrombopag (EPAG) had similar efficacy to CsA+ATG+EPAG. However, the adverse effects such as hepatotoxicity and gasrointestinal disorder limit its application in elderly SAA.Compared with EPAG, AVA has no hepatotoxicity and less other adverse effects, but there was few studies for AA. Our previous study demonstrated that AVA was effective in 55% of refractory AA. Since the action mechanism of AVA and EPAG is not exactly the same, and the metabolic level of the elderly is not the same as that of younger patients, it is unknown whether there are predictive factors of efficacy in the treatment of AVA. Thus, we wondered whether CsA+AVA could achieve an efficacy similar to CsA+ATG+AVA in the Elderly.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
86
Inclusion Criteria
  1. Patients with newly diagnosed severe aplastic anemia, aged greater than 60 years.
  2. Patients met the diagnostic criteria of severe aplastic anemia (SAA).
  3. Complete all screening assessments as outlined in the test protocol.
  4. Without or with no more than 1 month treatment of ciclosporine, tacrolimus, glucocortocoid, or TPO-RAs.
  5. Agree to sign the informed consent form.
Exclusion Criteria
  1. Known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of cytopenia.
  2. Patients with uncontrolled bleeding and/or infection despite standard treatment.
  3. Patients with previous history of hematopoietic stem cell transplantation.
  4. Patients with previous history of thrombosis in 1 year.
  5. Patients with concurrent malignancy.
  6. Those who are considered unsuitable for enrollment by the investigator.
  7. Abnormal renal function: creatinine > 1.2 normal upper limit, albumin < 0.9 normal lower limit, or CLcr < 30 ml/min.
  8. Abnormal liver function: transaminase > 2.5 normal upper limit, or tota bilirubin > 2.5 normal upper limit.
  9. Patients with severe heart, liver or renal disease.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CsA+AVAAvatrombopagCiclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
CsA+ATG+AVACiclosporinCiclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Anti-human thymocyte: rabbit anti-human thymocyte globulin (r-ATG 3mg/kg/d) was administered intravenously for 5 days; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
CsA+ATG+AVAAnti-Human Thymocyte Immunoglobulin, RabbitCiclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Anti-human thymocyte: rabbit anti-human thymocyte globulin (r-ATG 3mg/kg/d) was administered intravenously for 5 days; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
CsA+ATG+AVAAvatrombopagCiclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Anti-human thymocyte: rabbit anti-human thymocyte globulin (r-ATG 3mg/kg/d) was administered intravenously for 5 days; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
CsA+AVACiclosporinCiclosporine: 3-5 mg/kg/d orally, with ciclosporine trough concentrations maintained at 100-200 ng/ml for 3 months to achieve maximum efficacy and then tapered; Avatrombopag:60 mg/d orally, for a total of 24 weeks. Adjust the dose according to the platelet counts of patients.
Primary Outcome Measures
NameTimeMethod
Overall response rate6 month

Proportion of patient who achieved partial response or complete response

Secondary Outcome Measures
NameTimeMethod
Complete response rate6 month

Proportion of patient who achieved complete response (HGB\>100g/L, PLT\>100×109/L, ANC\>1.0×109/L)

Relapse rate12 month

Proportion of patient who relapse

Adverse event rate3, 6, 12 month

Proportion of patient who adverse events

Trial Locations

Locations (1)

Peking union medical college hospital

🇨🇳

Beijing, China

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