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

Aplastic Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06004752
• Other study ID #: Avatrombopag-2
• Status: Recruiting
• Phase: Phase 2
• Start date: August 17, 2023
• Est. completion date: August 2025

Study information

• Verified date: December 2023
• Source: Peking Union Medical College Hospital
• Contact: Bing Han
• Phone: +861069151235
• Email: hanbing_li[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2025
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Ciclosporin
Cyclosporine was taken orally at 3-5mg/kg bid was administered to maintain the trough concentration at 100-200 µg/ml
• 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.

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion	The change in hematology values ( haemoglobin) were evaluated	6 months
Secondary	Changes in Platelet in the Absence of Platelet Transfusion	The change in hematology values (platelet) were evaluated	6 months
Secondary	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
Secondary	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
Secondary	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