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

NCT05996393 | Completed Phase 4

• 1 other identifier: AVA-3
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

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.

Conditions

Aplastic Anemia

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Proportion of patient who achieved partial response or complete response

  6 month

Secondary Outcomes (3)

• Complete response rate

  6 month

• Relapse rate

  12 month

• Adverse event rate

  3, 6, 12 month

Study Arms (2)

CsA+ATG+AVA

EXPERIMENTAL

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; Drug: Avatrombopag; Drug: Anti-Human Thymocyte Immunoglobulin, Rabbit

CsA+AVA

EXPERIMENTAL

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; Drug: Avatrombopag

Interventions

Ciclosporin DRUG

3-5 mg/kg/d orally, trough concentrations: 100-200 ng/ml

CsA+ATG+AVA; CsA+AVA

Avatrombopag DRUG

60 mg/d orally, 24 weeks

CsA+ATG+AVA; CsA+AVA

Anti-Human Thymocyte Immunoglobulin, Rabbit DRUG

rabbit anti-human thymocyte immunoglobulin (r-ATG 3mg/kg/d), intravenously, 5 days;

CsA+ATG+AVA

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with newly diagnosed severe aplastic anemia, aged greater than 60 years.
• Patients met the diagnostic criteria of severe aplastic anemia (SAA).
• Complete all screening assessments as outlined in the test protocol.
• Without or with no more than 1 month treatment of ciclosporine, tacrolimus, glucocortocoid, or TPO-RAs.
• Agree to sign the informed consent form.

You may not qualify if:

• Known diagnosis of congenital hematopoietic failure disorders (e.g. Fanconi anemia) and other causes of cytopenia.
• Patients with uncontrolled bleeding and/or infection despite standard treatment.
• Patients with previous history of hematopoietic stem cell transplantation.
• Patients with previous history of thrombosis in 1 year.
• Patients with concurrent malignancy.
• Those who are considered unsuitable for enrollment by the investigator.
• Abnormal renal function: creatinine \> 1.2 normal upper limit, albumin \< 0.9 normal lower limit, or CLcr \< 30 ml/min.
• Abnormal liver function: transaminase \> 2.5 normal upper limit, or tota bilirubin \> 2.5 normal upper limit.
• Patients with severe heart, liver or renal disease.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking union medical college hospital

Beijing, China

Location

Related Publications (5)

• 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.

  PMID: 37160872 BACKGROUND

• 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.

  PMID: 36400314 BACKGROUND

• 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.

  PMID: 37318085 BACKGROUND

• 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.

  PMID: 33727526 BACKGROUND

• 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.

  PMID: 37271577 BACKGROUND

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

Cyclosporine; avatrombopag; Antilymphocyte Serum

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 18, 2023
• Study Start: September 15, 2023
• Primary Completion: February 20, 2025
• Study Completion: February 27, 2025
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)