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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: Ciclosporin; Drug: Avatrombopag; Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bing Han, Doctor; Phone Number: +86-010-69155760; Email: hanbing_li@sina.com.cn

Study Locations

• China
  • Beijing, China
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CsA+ATG+AVA; Ciclosporine: 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.	Drug: Ciclosporin; 3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml; Drug: Avatrombopag; 60 mg/d orally, 24 weeks; Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit; rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;
Experimental: CsA+AVA; Ciclosporine: 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.	Drug: Ciclosporin; 3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml; Drug: Avatrombopag; 60 mg/d orally, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate	Proportion of patient who achieved partial response or complete response	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	Proportion of patient who achieved complete response (HGB>100g/L, PLT>100×109/L, ANC>1.0×109/L)	6 month
Relapse rate	Proportion of patient who relapse	12 month
Adverse event rate	Proportion of patient who adverse events	3, 6, 12 month

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): October 1, 2025
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: August 1, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Bone Marrow Failure Disorders; Anemia; Anemia, Aplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; Thymoglobulin; Cyclosporine; Cyclosporins
• Other Study ID Numbers: AVA-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No