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

NCT ID: NCT05518331

Last Updated: 2022-08-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-01
• Study Completion Date: 2026-01-01

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%.

Conditions

Refractory Aplastic Anemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avatrombopag in RAA

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.

Group Type: EXPERIMENTAL

avatrombopag

Intervention Type: 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.

Interventions

avatrombopag

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.

Intervention Type: DRUG

Other Intervention Names

CSA

Eligibility Criteria

Inclusion 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

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.

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: collaborator

Xiyuan Hospital of China Academy of Chinese Medical Sciences

OTHER

Sponsor Role: collaborator

Second Hospital of Shanxi Medical University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Harbin Medical University

OTHER

Sponsor Role: collaborator

The First Hospital of Hebei Medical University

OTHER

Sponsor Role: collaborator

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Fengkui Zhang

Director of Anemia Treatment Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Liping Jing, Doctor

Role: STUDY_DIRECTOR

Anemia Treatment Center

Locations

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

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Fengkui Zhang, Doctor

Role: CONTACT

fkzhang@ihcams.ac.cn

8602223909229

Liping Jing, Doctor

Role: CONTACT

jingliping@ihcams.ac.an

8602223909223

Facility Contacts

Fengkui Zhang, Doctor

Role: primary

fkzhang@ihcams.ac.cn

8602223909229

Liping Jing, Doctor

Role: backup

jingliping@ihcams.ac.cn

8602223909223

References

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.

Reference Type: RESULT

PMID: 26568159 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30504345 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28423296 (View on PubMed)

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.

Reference Type: RESULT

PMID: 22762314 (View on PubMed)

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.

Reference Type: RESULT

PMID: 35371427 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32876852 (View on PubMed)

Other Identifiers

IIT2021008-EC-1

Identifier Type: -

Identifier Source: org_study_id