Efficacy and Safety of CsA+AVA in the Treatment of NSAA in the Elderly

A Single-center, Single-arm, Prospective Clinical Study on the Efficacy and Safety of Cyclosporine Combined With Avatrombopag in the Treatment of Non-severe Aplastic Anemia in the Elderly

For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag (AVA), which has a slight adverse reaction, can theoretically improve the hematological response rate in elderly patients with non-severe aplastic anemia (NSAA) without significantly increasing adverse reactions. Based on this, this study treated NSAA patients older than 60 with AVA combined with CsA to evaluate the hematological response rate and safety of AVA in the elderly who could not tolerate ATG therapy.

Study Overview

• Status: Recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: Ciclosporin; Drug: Avatrombopag

Detailed Description

Aplastic anemia (AA) can be divided into severe AA (SAA) and non-severe AA (NSAA), according to the severity of the disease. Anti-thymocyte globulin (ATG) in combination with CsA is the most typical combined immunosuppressive therapy regimen. For elderly patients who cannot tolerate anti-thymocyte globulin (ATG) treatment, the addition of avatrombopag, which has a slight adverse reaction, can theoretically improve the hematological response rate in elderly patients with NSAA without significantly increasing adverse reactions. Based on this, this study treated NSAA patients older than 60 with AVA combined with CsA to evaluate the hematological response rate and safety of AVA in the elderly who could not tolerate ATG therapy.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Bing Han; Phone Number: +861069151235; Email: hanbing_li@sina.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Bing Han, Doctor; Phone Number: +86-010-69155760; Email: hanbing_li@sina.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Elderly patients with well-defined NSAA anemia who meet the diagnostic criteria for aplastic anemia (AA) but do not meet the diagnostic criteria for severe aplastic anemia (SAA).
2. Age 60 years or older, male or female.
3. Able to swallow or administer orally.
4. Intolerant or refused anti-thymocyte globulin treatment

6. No previous treatment with cyclosporine, tacrolimus or hormones or treatment for less than 1 month.

7. No prior treatment with thrombopoietin (TPO) receptor agonists (including eltrombopag, herombopag, romiplostim, etc.) 8. Informed consent must be signed before the start of all specific research procedures. Considering the patient's condition, if the patient's signature is not conducive to the treatment of the disease, the informed consent shall be signed by the patient's immediate family.

Exclusion Criteria:

1. Known congenital AA (such as Fanconi anemia) and other causes of pancytopenia and hematological bone marrow disorders;
2. With paroxysmal nocturnal hemoglobinuria (PNH) clone ≥ 50%
3. With a history of hematopoietic stem cell transplantation.
4. History of thrombosis
5. Patients with underlying cancer who also have malignant tumors or are receiving immunosuppressive therapy.
6. Baseline creatine levels greater than twice of the upper limit of normal (ULN) and/or alanine aminotransferase (ALT) greater than 2.5 times of the ULN;
7. Serious heart, liver and kidney disease.
8. With uncontrolled bleeding and/or infection after standard treatment.
9. Participants considered unsuitable for inclusion by the researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment group; Cyclosporine: 3mg/kg/d 3-5mg/kg bid was administered to maintain the trough concentration at 100-200 μg/ml; Avatrombopag: The dosage was 40~60mg orally, once a day, and the dosage was adjusted according to the subject's platelet count. The drug was administered for 24 weeks (6 months).

Drug: Ciclosporin; Cyclosporine was taken orally at 3-5mg/kg bid was administered to maintain the trough concentration at 100-200 μg/ml; Drug: Avatrombopag; Avatrombopag was administrated at 40 mg/d and increased by 20 mg/d during the biweekly follow-up if platelet was not 20 × 109/L higher than baseline. AVA dose was gradually reduced if PLT ≥ 150 × 109/L. The maximum dose was 60 mg/d, while the minimum was 20 mg/week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR at 6 Months	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia	Clonal evolution to myelodysplasia is defined as a new marrow cytogenic abnormality with or without characteristic dysplastic marrow findings. Evolution to leukemia is defined as greater than 20% peripheral blood and/or marrow blasts. Evolution to paroxysmal nocturnal hemoglobinuria (PNH) is defined as a clone at baseline < 10% that rose to greater than 50% on study.	12 months
Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion	The change in hematology values ( haemoglobin) were evaluated	6 months
Changes in Platelet in the Absence of Platelet Transfusion	The change in hematology values (platelet) were evaluated	6 months
ORR at 1, 2, 3 Months and at the end of follow-up	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR)	1, 2, 3 Months, last follow-up
Relapse rate	Relapse was defined as a substantial or progressive decline in at least one blood lineage counts of the responders that required the reinitiation or augmentation of AVA.	6 months, last follow-up

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: August 16, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 2, 2023
• Last Verified: December 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; Cyclosporine; Cyclosporins
• Other Study ID Numbers: Avatrombopag-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: individual participant data would be accepted upon request
• IPD Sharing Time Frame: always
• IPD Sharing Access Criteria: email request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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