Clinical trial NCT06426043: A Prospective Study on the Treatment of Recurrent/Refractory/Intolerable NSAA With Lusutrombopag
Official title: An Exploratory Study on the Efficacy and Safety of Lusutrombopag in the Treatment of Recurrent/Refractory/Intolerable NSAA
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Aplastic Anemia
Keywords: Non-severe aplastic anemia
Lusutrombopag
Refractory
Recurrent
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2024-05-23
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate at 3 months
timeFrame: 3 month
measure: Overall response rate at 6 months
timeFrame: 6 month
Secondary outcomes:
measure: adverse event rate at 3 months
timeFrame: 3 month
measure: adverse event rate at 6 months
timeFrame: 6 month
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Bing Bing, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Young NS. Aplastic Anemia. N Engl J Med. 2018 Oct 25;379(17):1643-1656. doi: 10.1056/NEJMra1413485. No abstract available.
citation: 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.
citation: 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.
citation: 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.
citation: 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.