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

NCT05518331 | Unknown

• 1 other identifier: IIT2021008-EC-1
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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

Conditions

Refractory Aplastic Anemia

Keywords

Avatrombopag, TPO-RA, refractory aplastic anemia

Outcome Measures

Primary Outcomes (3)

• The rate of HR in patients after switching to avatrombopag.

  Percentage of the total number of patients receiving treatment who received APAG

  3 months

• Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading

  Incidence of Treatment-Emergent AE by CTCAE

  3 months

• Percentage of patients with transformation

  Rate of patients with transformation to PNH or MDS,AML, or other disease

  3 months

Secondary Outcomes (6)

• The rate of HR in patients after switching to avatrombopag.

  6months

• ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading

  6months

• Percentage of patients with transformation

  6months

• The rate of HR in patients after switching to avatrombopag.

  12months

• ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading

  12months

Study Arms (1)

Avatrombopag in RAA

EXPERIMENTAL

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.

Drug: avatrombopag

Interventions

avatrombopag DRUG

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.

Also known as: CSA

Avatrombopag in RAA

Eligibility Criteria

• Age: 14 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead
• Peking University People's Hospital: collaborator
• Xiyuan Hospital of China Academy of Chinese Medical Sciences: collaborator
• Second Hospital of Shanxi Medical University: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• The First Hospital of Hebei Medical University: collaborator

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 26568159 RESULT

• 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.

  PMID: 30504345 RESULT

• 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.

  PMID: 28423296 RESULT

• 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.

  PMID: 22762314 RESULT

• 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.

  PMID: 35371427 RESULT

• 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.

  PMID: 32876852 RESULT

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

avatrombopag

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Study Officials

• Liping Jing, Doctor

  Anemia Treatment Center

  STUDY DIRECTOR

Central Study Contacts

Fengkui Zhang, Doctor

CONTACT

8602223909229; fkzhang@ihcams.ac.cn

Liping Jing, Doctor

CONTACT

8602223909223; jingliping@ihcams.ac.an

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Anemia Treatment Center

Study Record Dates

• First Submitted: June 11, 2022
• First Posted: August 26, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2025
• Study Completion: January 1, 2026
• Last Updated: August 26, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: Follow-up and publication of the paper are planned for December 2025
• Access Criteria: After the paper is written and published

Locations

CN (1)