Back to resultsThe Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA
Primary Purpose
Refractory Aplastic Anemia
Status
Recruiting
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
avatrombopag
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Aplastic Anemia focused on measuring Avatrombopag, TPO-RA, refractory aplastic anemia
Eligibility Criteria
Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria:
- 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
- Age > 14 years old, male or female.
- Subjects must complete all screening assessments listed in the trial protocol.
- ECOG score ≤ 2 points.
- 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:
- Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, various bacterial and viral infections) and active bleeding that cannot be controlled after standard treatment.
- Patients with AIDS, active viral hepatitis B, and hepatitis C RNA nucleic acid test positive.
- Those who are pregnant or breastfeeding, have fertility but are unwilling to take effective contraceptive measures.
- Congenital hematopoietic failure diseases (such as Fanconi anemia).
- Patients with cytogenetic clonal changes (excluding germline mutations and acquired chromosome clones of +8, 20q- and -y).
- Combined with malignant tumor within 3 years.
- Combined with other systemic diseases that cannot be controlled.
- Significant abnormalities in cardiopulmonary function.
- 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.
- Those who are considered unsuitable for enrollment by the investigator.
Sites / Locations
- Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical SciencesRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Avatrombopag in RAA
Arm Description
After the patients met the above-mentioned inclusion conditions and signed informed consent, they began to be included in this program. The main research objectives are to take avatrombopag conversion therapy for at least 3 months, to monitor hematological indicators, biochemical indicators and bone marrow related tests, to determine hematological responses, and to evaluate the safety of the drug. In the 6th and 12th months after treatment, comprehensive review of bone marrow and peripheral blood was performed to evaluate the recovery of hematopoiesis, determine the curative effect, evaluate adverse events, and whether there was clonal transformation. After the patients completed the main study observation, they were followed up for at least 3 months, that is, from the time the patients were enrolled, for a total of at least 6 months of follow-up.
Outcomes
Primary Outcome Measures
The rate of HR in patients after switching to avatrombopag.
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
Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation
Rate of patients with transformation to PNH or MDS,AML, or other disease
Secondary Outcome Measures
The rate of HR in patients after switching to avatrombopag.
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
Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation
Rate of patients with transformation to PNH or MDS,AML, or other disease
The rate of HR in patients after switching to avatrombopag.
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
Incidence of Treatment-Emergent AE by CTCAE
Percentage of patients with transformation
Rate of patients with transformation to PNH or MDS,AML, or other disease
Full Information
NCT ID
NCT05518331
First Posted
June 11, 2022
Last Updated
August 25, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Peking University People's Hospital, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Second Hospital of Shanxi Medical University, First Affiliated Hospital of Harbin Medical University, The First Hospital of Hebei Medical University
1. Study Identification
Unique Protocol Identification Number
NCT05518331
Brief Title
The Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA
Official Title
Avatrombopag in TPO-RA Refractory Aplastic Anemia Patients Safety and Efficacy Study --Single-arm, Multicenter, Open, Phase Π Clinical Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2022 (Actual)
Primary Completion Date
June 1, 2025 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Peking University People's Hospital, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Second Hospital of Shanxi Medical University, First Affiliated Hospital of Harbin Medical University, The First Hospital of Hebei Medical University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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%.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Aplastic Anemia
Keywords
Avatrombopag, TPO-RA, refractory aplastic anemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
39 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Avatrombopag in RAA
Arm Type
Experimental
Arm Description
After the patients met the above-mentioned inclusion conditions and signed informed consent, they began to be included in this program.
The main research objectives are to take avatrombopag conversion therapy for at least 3 months, to monitor hematological indicators, biochemical indicators and bone marrow related tests, to determine hematological responses, and to evaluate the safety of the drug.
In the 6th and 12th months after treatment, comprehensive review of bone marrow and peripheral blood was performed to evaluate the recovery of hematopoiesis, determine the curative effect, evaluate adverse events, and whether there was clonal transformation.
After the patients completed the main study observation, they were followed up for at least 3 months, that is, from the time the patients were enrolled, for a total of at least 6 months of follow-up.
Intervention Type
Drug
Intervention Name(s)
avatrombopag
Other Intervention Name(s)
CSA
Intervention Description
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.
Primary Outcome Measure Information:
Title
The rate of HR in patients after switching to avatrombopag.
Description
Percentage of the total number of patients receiving treatment who received APAG
Time Frame
3 months
Title
Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading
Description
Incidence of Treatment-Emergent AE by CTCAE
Time Frame
3 months
Title
Percentage of patients with transformation
Description
Rate of patients with transformation to PNH or MDS,AML, or other disease
Time Frame
3 months
Secondary Outcome Measure Information:
Title
The rate of HR in patients after switching to avatrombopag.
Description
Percentage of the total number of patients receiving treatment who received APAG
Time Frame
6months
Title
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading
Description
Incidence of Treatment-Emergent AE by CTCAE
Time Frame
6months
Title
Percentage of patients with transformation
Description
Rate of patients with transformation to PNH or MDS,AML, or other disease
Time Frame
6months
Title
The rate of HR in patients after switching to avatrombopag.
Description
Percentage of the total number of patients receiving treatment who received APAG
Time Frame
12months
Title
ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading
Description
Incidence of Treatment-Emergent AE by CTCAE
Time Frame
12months
Title
Percentage of patients with transformation
Description
Rate of patients with transformation to PNH or MDS,AML, or other disease
Time Frame
12months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
14 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria:
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
Age > 14 years old, male or female.
Subjects must complete all screening assessments listed in the trial protocol.
ECOG score ≤ 2 points.
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:
Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, various bacterial and viral infections) and active bleeding that cannot be controlled after standard treatment.
Patients with AIDS, active viral hepatitis B, and hepatitis C RNA nucleic acid test positive.
Those who are pregnant or breastfeeding, have fertility but are unwilling to take effective contraceptive measures.
Congenital hematopoietic failure diseases (such as Fanconi anemia).
Patients with cytogenetic clonal changes (excluding germline mutations and acquired chromosome clones of +8, 20q- and -y).
Combined with malignant tumor within 3 years.
Combined with other systemic diseases that cannot be controlled.
Significant abnormalities in cardiopulmonary function.
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.
Those who are considered unsuitable for enrollment by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fengkui Zhang, Doctor
Phone
8602223909229
Email
fkzhang@ihcams.ac.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Liping Jing, Doctor
Phone
8602223909223
Email
jingliping@ihcams.ac.an
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Liping Jing, Doctor
Organizational Affiliation
Anemia Treatment Center
Official's Role
Study Director
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fengkui Zhang, Doctor
Phone
8602223909229
Email
fkzhang@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Liping Jing, Doctor
Phone
8602223909223
Email
jingliping@ihcams.ac.cn
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We can share the plan after completing the experiment
IPD Sharing Time Frame
Follow-up and publication of the paper are planned for December 2025
IPD Sharing Access Criteria
After the paper is written and published
Citations:
PubMed Identifier
26568159
Citation
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016 Jan;172(2):187-207. doi: 10.1111/bjh.13853. Epub 2015 Nov 16. No abstract available. Erratum In: Br J Haematol. 2016 Nov;175(3):546.
Results Reference
result
PubMed Identifier
30504345
Citation
Scheinberg P. Activity of eltrombopag in severe aplastic anemia. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):450-456. doi: 10.1182/asheducation-2018.1.450.
Results Reference
result
PubMed Identifier
28423296
Citation
Townsley DM, Scheinberg P, Winkler T, Desmond R, Dumitriu B, Rios O, Weinstein B, Valdez J, Lotter J, Feng X, Desierto M, Leuva H, Bevans M, Wu C, Larochelle A, Calvo KR, Dunbar CE, Young NS. Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med. 2017 Apr 20;376(16):1540-1550. doi: 10.1056/NEJMoa1613878.
Results Reference
result
PubMed Identifier
22762314
Citation
Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931. Erratum In: N Engl J Med. 2012 Jul 19;367(3):284.
Results Reference
result
PubMed Identifier
35371427
Citation
Peng G, He G, Chang H, Gao S, Liu X, Chen T, Li P, Han B, Miao M, Ge Z, Ge X, Li F, Li Y, Wang S, Wang Y, Shen Y, Zhang T, Zou J, Zhang F. A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy. Ther Adv Hematol. 2022 Mar 30;13:20406207221085197. doi: 10.1177/20406207221085197. eCollection 2022.
Results Reference
result
PubMed Identifier
32876852
Citation
Ise M, Iizuka H, Kamoda Y, Hirao M, Kida M, Usuki K. Romiplostim is effective for eltrombopag-refractory aplastic anemia: results of a retrospective study. Int J Hematol. 2020 Dec;112(6):787-794. doi: 10.1007/s12185-020-02971-1. Epub 2020 Sep 2.
Results Reference
result
Learn more about this trial
The Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA
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