Clinical trial NCT05996393: CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly
Official title: Ciclosporin + Antithymocyte Immunoglobulin + Avatrombpag Versus Ciclosporin + Avatrombpag for the Treatment of Severe Aplastic Anemia in the Elderly
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aplastic Anemia
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2023-08-18
Enrollment: 86
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate
timeFrame: 6 month
Secondary outcomes:
measure: Complete response rate
timeFrame: 6 month
measure: Relapse rate
timeFrame: 12 month
measure: Adverse event rate
timeFrame: 3, 6, 12 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
References:
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citation: Chi Y, Hu Q, Yang C, Chen M, Han B. Avatrombopag is effective in patients with chemoradiotherapy-induced aplastic anemia: a single-center, retrospective study. Exp Hematol. 2023 Jan;117:62-68. doi: 10.1016/j.exphem.2022.11.002. Epub 2022 Nov 16.
citation: Wan Z, Chen M, Han B. Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial. Ann Med. 2023 Dec;55(1):2224044. doi: 10.1080/07853890.2023.2224044.
citation: Chen F, Hu S, Ruan J, Chen M, Han B. Mutational landscape and its clinical significance in paroxysmal nocturnal hemoglobinuria. Blood Cancer J. 2021 Mar 16;11(3):58. doi: 10.1038/s41408-021-00451-1. No abstract available.
citation: Chen M, Liu Q, Gao Y, Suo X, Ding X, Wang L, Li L, Shao Y, Gao D, Sun W, Tan Y, Wang W, Ye F, Han B. Cyclosporine plus eltrombopag in the treatment of aplastic anemia with or without antithymocyte immunoglobulin: A multicenter real-world retrospective study. Eur J Haematol. 2023 Sep;111(3):407-413. doi: 10.1111/ejh.14021. Epub 2023 Jun 4.