The Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA

Conditions

Refractory Aplastic Anemia

Keywords

Avatrombopag, TPO-RA, refractory aplastic anemia

Brief summary

This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight \<80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight \<80 kg; 60 mg daily for weight \>80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug

Detailed description

This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight \<80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight \<80 kg; 60 mg daily for weight \>80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug.Selection of study population Severe aplastic anemia patients with poor efficacy of IST combined with TPO-RA Patients should be judged for inclusion and exclusion criteria. Number of subjects: 35 effective cases, 39 patients should be included according to the dropout rate of 10%.

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Interventions

DRUGavatrombopag

Avatrombopag, 40-60 mg (body weight \< 80 kg, 40 mg per day; body weight \> 80 kg, 60 mg per day) orally once daily for at least 3 months and followed up for 3 months to determine hematological response and evaluate the drug security.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

14 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Subjects eligible for inclusion in this study must meet all of the following criteria: 1. Patients with confirmed TDNSAA/SAA/VSAA aplastic anemia who received standard IST therapy for at least 6 months, combined with Haitrombopag (15mg/d) or Eltrombopag (\>50mg/d) for at least 3 Patients who have not obtained a hematological response (NR) for months and are not suitable or unwilling to undergo HSCT 2. Age \> 14 years old, male or female. 3. Subjects must complete all screening assessments listed in the trial protocol. 4. ECOG score ≤ 2 points. 5. Before the start of the research procedure, the patient or guardian should fully understand the research procedure and purpose and sign the informed consent form. If the patient's signature is not conducive to the treatment of the disease, the patient's immediate family should sign the informed consent form.

Exclusion criteria

Subjects meeting any of the following criteria were excluded from this study: 1. Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, various bacterial and viral infections) and active bleeding that cannot be controlled after standard treatment. 2. Patients with AIDS, active viral hepatitis B, and hepatitis C RNA nucleic acid test positive. 3. Those who are pregnant or breastfeeding, have fertility but are unwilling to take effective contraceptive measures. 4. Congenital hematopoietic failure diseases (such as Fanconi anemia). 5. Patients with cytogenetic clonal changes (excluding germline mutations and acquired chromosome clones of +8, 20q- and -y). 6. Combined with malignant tumor within 3 years. 7. Combined with other systemic diseases that cannot be controlled. 8. Significant abnormalities in cardiopulmonary function. 9. Abnormal liver and kidney function: creatinine level \> 1.5 times the upper limit of normal, transaminase and bilirubin level \> 2 times the upper limit of normal, and those who cannot be enrolled in the group as judged by the clinician. 10. Those who are considered unsuitable for enrollment by the investigator.

Design outcomes

Primary

Measure	Time frame	Description
The rate of HR in patients after switching to avatrombopag.	3 months	Percentage of the total number of patients receiving treatment who received APAG
Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading	3 months	Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation	3 months	Rate of patients with transformation to PNH or MDS,AML, or other disease

Secondary

Measure	Time frame	Description
The rate of HR in patients after switching to avatrombopag.	6months	Percentage of the total number of patients receiving treatment who received APAG
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading	6months	Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation	6months	Rate of patients with transformation to PNH or MDS,AML, or other disease

Countries

China

Contacts

Primary ContactFengkui Zhang, Doctor

fkzhang@ihcams.ac.cn8602223909229

Backup ContactLiping Jing, Doctor

jingliping@ihcams.ac.an8602223909223

Outcome results

None listed