A Single-center, Single-arm, Prospective Clinical Study on the Efficacy and Safety of CsA+AVA in the Treatment of NSAA in the Elderly
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: treatment group Cyclosporine: 3mg/kg/d orally divided into two times, the valley concentration of cyclosporine maintained at 100~150ng/ml, to achieve the maximum effect and began to reduce after 3 months, the reduction of 25mg every 3 months; 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: Avatrombopag+CsA
Cyclosporine was taken orally at 3mg/kg/d twice, and the valley concentration of cyclosporine was maintained at 100-150ng /ml.
Avatrombopag：The dosage is 40~60mg, once a day, orally.(If the patient has a hematological reaction and platelets rapidly rise to PLT>200×10^9/L, the drug should be stopped and observed until the PLT<100×109/L and then reduced by one titration dose; If the platelet recovered to 100-200 ×10^9/L for more than 2 months, the titration dose was reduced by one. After the reduction to 20mg, platelets can still be maintained at 100~200×10^9/L, and for more than 2 months, the reduction to 20mg 1/ every other day; After the reduction, platelets can still be maintained at 100-200 ×10^9/L for more than 2 months
|
Outcome Measures
Primary Outcome Measures
- ORR at 6 Months [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) at Week 26
Secondary Outcome Measures
- Changes in Haemoglobin in the Absence of Red Blood Cells Transfusion [6 months]
The change in hematology values ( haemoglobin) were evaluated
- Changes in Platelet in the Absence of Platelet Transfusion [6 months]
The change in hematology values (platelet) were evaluated
- Percentage of patients with clonal evolution to myelodysplasia, PNH, acute leukemia [12 months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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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). AA is diagnosed if at least two of the following conditions are met: hemoglobin <100 g/L, platelet count <50×109/L, and neutrophil count <1.5×109/L. SAA diagnostic criteria: Meet the following diagnostic criteria, at least two of the following three criteria meet PLT < 20×109/L, ANC < 0.5×109/L, ARC < 60×109/L or red blood cell corrected volume <1%.
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Age 65 years or older, male or female.
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Subjects must complete all screening assessments listed in the trial protocol.
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Able to swallow or administer orally.
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Cannot tolerate or refuse ATG treatment.
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No previous treatment with cyclosporine, tacrolimus or hormones or treatment for less than 1 month.
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No TPO receptor agonists (including thrombopoietin, aitripopar, tritripopar, etc.) were used or TPO receptor agonists were used to treat the total dose of thrombopoietin, Eltrombopag, Herombopag, Avatrombopag and other TPO receptor agonists ≤1 week.
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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:
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Known congenital hematopoietic exhaustion diseases (such as Fanconi anemia) and other causes of pancytopenia and bone marrow hypoproliferative diseases (such as hemolytic PNH, hypoproliferative MDS/AML, autoantibody-mediated pancytopenia, etc.);
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Patients with uncontrolled bleeding and/or infection after standard treatment.
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Patients with a history of hematopoietic stem cell transplantation.
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History of high blood pressure.
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History of thrombosis.
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Patients with underlying cancer who also have malignant tumors or are receiving immunosuppressive therapy.
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Participants considered unsuitable for inclusion by the researchers.
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Renal function indicators: serum creatinine >1.2 times the upper limit of normal (ULN) or albumin <0.9 times the lower limit of normal (LLN); Patients with severe renal insufficiency with creatinine clearance <30ml/min;
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Liver function indicators: alanine aminotransferase (ALT) is 2.5 times higher than the upper limit of normal or AST is 2.5 times higher than the upper limit of normal or total bilirubin is 2.5 times higher than the upper limit of normal or serum creatinine is 1.5 times higher than the upper limit of normal;
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Serious heart, liver and kidney disease.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking union medical college hospital | Beijing | China |
Sponsors and Collaborators
- Peking Union Medical College Hospital
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Avatrombopag-2