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

Aplastic Anemia Clinical Trial

Official title:

Ciclosporin + Antithymocyte Immunoglobulin + Avatrombpag Versus Ciclosporin + Avatrombpag for the Treatment of Severe Aplastic Anemia in the Elderly

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05996393
• Other study ID #: AVA-3
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: October 2023
• Est. completion date: October 2026

Study information

• Verified date: August 2023
• Source: Peking Union Medical College Hospital
• Contact: Bing Han, Doctor
• Phone: +86-010-69155760
• Email: hanbing_li[@]sina.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: October 2026
• Est. primary completion date: October 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Ciclosporin
3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml
• Avatrombopag
60 mg/d orally, 24 weeks
• Anti-Human Thymocyte Immunoglobulin, Rabbit
rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;

Locations

Country	Name	City	State
China	Peking union medical college hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

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. Erratum In: Blood Cancer J. 2021 May 6;11(5):85. — View 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 Jun 4. doi: 10.1111/ejh.14021. Online ahead of print. — View 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. — View 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. — View Citation

Yang Y, Tang Z, Huang Y, Hu Q, Wang S, Ji J, Du Y, Yang C, Chen M, Hu S, Han B. Sirolimus versus cyclosporine A in patients with primary acquired pure red cell aplasia: a prospective cohort study. Blood Cancer J. 2023 May 10;13(1):74. doi: 10.1038/s41408-023-00845-3. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate	Proportion of patient who achieved partial response or complete response	6 month
Secondary	Complete response rate	Proportion of patient who achieved complete response (HGB>100g/L, PLT>100×109/L, ANC>1.0×109/L)	6 month
Secondary	Relapse rate	Proportion of patient who relapse	12 month
Secondary	Adverse event rate	Proportion of patient who adverse events	3, 6, 12 month