Aplastic Anemia
Conditions
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.
Interventions
rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;
DRUGCiclosporin
3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml
DRUGAvatrombopag
60 mg/d orally, 24 weeks
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 6 month | Proportion of patient who achieved partial response or complete response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate | 6 month | Proportion of patient who achieved complete response (HGB\>100g/L, PLT\>100×109/L, ANC\>1.0×109/L) |
| Relapse rate | 12 month | Proportion of patient who relapse |
| Adverse event rate | 3, 6, 12 month | Proportion of patient who adverse events |
Countries
China
Outcome results
None listed