A Prospective Study on the Treatment of Recurrent/Refractory/Intolerable NSAA With Lusutrombopag

An Exploratory Study on the Efficacy and Safety of Lusutrombopag in the Treatment of Recurrent/Refractory/Intolerable NSAA

In a prospective, single-arm study, the efficacy and safety of Lusutrombopag in the treatment of relapsed/refractory/intolerable non-severe aplastic anemia (NSAA) were explored.

Study Overview

• Status: Not yet recruiting
• Conditions: Aplastic Anemia
• Intervention / Treatment: Drug: Lusutrombopag

Detailed Description

The enrolled patients: were given Lusutrombopag at 3mg/qd orally for 12 weeks (the starting dose of lusutrombopag was 3mg, taken once daily. After 2 weeks of continuous administration, the dose was increased by 3mg every 2 weeks based on the platelet count and safety of the subjects. The dose was gradually increased to 9mg/d over a total of 12 weeks). The treatment duration was at least 3 months. When the platelet increase was <20×10^9/L, the daily dose was increased by 3mg, up to a maximum of 9mg/day. When the platelet increase was ≥50×109/L and ≤200×10^9/L, the dose was maintained at the previous level. When the platelet count was ≥200×10^9/L and ≤400×10^9/L, the daily dose was reduced by 3mg. When the platelet count was >400×10^9/L, the drug could be suspended, and the dose was reduced by 3mg when the platelet count decreased to <200×10^9/L. In this case, if the lowest dose of 3mg/day was used, the drug could be suspended. Responders continued treatment for 6 months. Other TPO-RA therapies were not allowed during the study period.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bing Bing, PhD; Phone Number: 13601059938; Email: Hanbing_li@sina.com.cn
• Study Contact Backup: Name: QLin Hu, PhD; Phone Number: 15810785167; Email: HQLin2012@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
      • Contact: QLin Hu, PhD; Phone Number: 15810785167; Email: HQLin2012@163.com
      • Principal Investigator: Bing Bing, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants must be at least 18 years old, male or female.
2. Participants must be diagnosed with NSAA and have a refractory/relapsed/intolerable response to standard-dose cyclosporine (CsA). The definition of refractory/relapsed is patients who have been treated with sufficient doses of cyclosporine (3-5mg/kg) for at least 6 months without response or relapse. The definition of intolerable is patients who cannot tolerate CsA and have stopped treatment due to significant side effects.
3. Participants must meet the following criteria at enrollment: platelets <30×109/L.
4. Baseline liver and kidney function must be within 2 times of normal range.
5. No active infection; no pregnancy or breastfeeding.
6. Participants must agree to sign the informed consent form.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

Exclusion Criteria:

1. Other causes of pancytopenia, such as myelodysplastic syndrome (MDS).
2. Evidence of clonal hematopoietic system bone marrow disease (MDS, AML) with cytogenetics.
3. PNH clone ≥50%.
4. Received hematopoietic stem cell transplant (HSCT) prior to enrollment.
5. Received ATG treatment within 6 months prior to enrollment.
6. Infection or bleeding that cannot be controlled with standard therapy.
7. Allergic to ruxolitinib.
8. Active HIV, HCV, or HBV infection, cirrhosis, or portal hypertension.
9. Any malignant tumor within 5 years, or local basal cell carcinoma of the skin.
10. History of thromboembolic events, myocardial infarction, or stroke (including antiphospholipid syndrome) and current use of anticoagulants.
11. Pregnant or breastfeeding (lactating) women.
12. Participated in another clinical trial within 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Lusutrombopag; Administer lusutrombopag at 3mg/qd orally for 12 weeks (lusutrombopag starting dose is 3mg, once daily. After 2 weeks of continuous administration, the dose can be increased by 3mg every 2 weeks based on the platelet count and safety of the subject. The dose can be gradually increased to 9mg/d over a total of 12 weeks). The course should be at least 3 months. When the platelet increase is <20×10^9/L, the daily dose can be increased by 3mg up to a maximum of 9mg/day; when the platelet increase is ≥50×10^9/L and ≤200×10^9/L, the dose can be maintained; when the platelet count is ≥200×10^9/L and ≤400×10^9/L, the daily dose can be reduced by 3mg; when the platelet count is >400×10^9/L, the drug can be suspended and resumed when the platelet count decreases to <200×10^9/L, with the daily dose reduced by 3mg. In this case, if the lowest dose of 3mg/day is used, the drug can be suspended. Responders continue treatment until 6 months.

Drug: Lusutrombopag; Administer lusutrombopag at 3mg/qd orally for 12 weeks (lusutrombopag starting dose is 3mg, once daily. After 2 weeks of continuous administration, the dose can be increased by 3mg every 2 weeks based on the platelet count and safety of the subject. The dose can be gradually increased to 9mg/d over a total of 12 weeks). The course should be at least 3 months. When the platelet increase is <20×109/L, the daily dose can be increased by 3mg up to a maximum of 9mg/day; when the platelet increase is ≥50×10^9/L and ≤200×10^9/L, the dose can be maintained; when the platelet count is ≥200×10^9/L and ≤400×10^9/L, the daily dose can be reduced by 3mg; when the platelet count is >400×10^9/L, the drug can be suspended and resumed when the platelet count decreases to <200×10^9/L, with the daily dose reduced by 3mg. In this case, if the lowest dose of 3mg/day is used, the drug can be suspended. Responders continue treatment until 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate at 3 months	Proportion of patients who achieved complete response, partial response and hematological response	3 month
Overall response rate at 6 months	Proportion of patients who achieved complete response, partial response and hematological response	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event rate at 3 months	Proportion of patients with adverse eventsProportion of patients with adverse events	3 month
adverse event rate at 6 months	Proportion of patients with adverse events	6 month

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Bing Bing, PhD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Wan Z, Chen M, Han B. Avatrombopag, a promising novel thrombopoietin receptor agonist for refractory/relapsed/intolerant non-severe aplastic anemia: a phase 2 single-arm clinical trial. Ann Med. 2023 Dec;55(1):2224044. doi: 10.1080/07853890.2023.2224044.
• Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.
• Ruan J, Zuo W, Chen M, Yang C, Han B. Eltrombopag is effective in patients with relapse/refractory aplastic anemia-report from a single center in China. Ann Hematol. 2020 Dec;99(12):2755-2761. doi: 10.1007/s00277-020-04266-1. Epub 2020 Sep 17. Erratum In: Ann Hematol. 2020 Nov 2;:
• Katsube T, Wajima T, Fukuhara T, Kano T. Effects of Food and Calcium Carbonate on the Pharmacokinetics of Lusutrombopag, a Novel Thrombopoietin Receptor Agonist. Clin Ther. 2019 Sep;41(9):1747-1754.e2. doi: 10.1016/j.clinthera.2019.06.004. Epub 2019 Jul 11.
• Hidaka H, Kurosaki M, Tanaka H, Kudo M, Abiru S, Igura T, Ishikawa T, Seike M, Katsube T, Ochiai T, Kimura K, Fukuhara T, Kano T, Nagata T, Tanaka K, Kurokawa M, Yamamoto K, Osaki Y, Izumi N, Imawari M. Lusutrombopag Reduces Need for Platelet Transfusion in Patients With Thrombocytopenia Undergoing Invasive Procedures. Clin Gastroenterol Hepatol. 2019 May;17(6):1192-1200. doi: 10.1016/j.cgh.2018.11.047. Epub 2018 Nov 28.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Refractory; Recurrent; Lusutrombopag; Non-severe aplastic anemia
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Anemia; Bone Marrow Failure Disorders; Anemia, Aplastic
• Other Study ID Numbers: LNA-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No