Hetrombopag for Low/Intermediate-1 Risk MDS With Thrombocytopenia

MDS Clinical Trial

Official title:

The Efficacy and Safety of Hetrombopag for Low/Intermediate-1 Risk MDS With Thrombocytopenia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05024877
• Other study ID #: HBP-MDS-001
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: October 1, 2021
• Est. completion date: December 1, 2023

Study information

• Verified date: September 2021
• Source: Peking Union Medical College Hospital
• Contact: Bing Han, Docter
• Phone: +8613601059938
• Email: hanbing_li[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Myelodysplastic syndrome (MDS) is a kind of clonal myeloid tumor. The major manifestation is decrease of tri-lineages of blood due to ineffective and abnormal hematopoiesis, some of which can progress to acute myeloid leukemia. According to the international prognosis scoring system (IPSS) of MDS, about 10% low/intermediate risk-1 MDS patients have severe thrombocytopenia (PLT < 30 × 109/ L). These patients have both decreased platelet count and platelet dysfunction, resulting in a high risk of bleeding. In the new prognostic score, such as IPSS-r, the degree of thrombocytopenia is regarded as a poor prognostic factor. Platelet transfusion is mainly used in the treatment of this kind of patients. The indications of transfusion include bleeding events or severe platelet count reduction (< 10 × 109 / L). However, platelet transfusion can only lead to short-term platelet elevation, while repeated transfusion increases the possibility of infection and ineffective platelet transfusion. TPO is a newly discovered hematopoietic promoting factor, which can specifically bind to the TPO receptor on the cell and participate in the regulation of proliferation, differentiation, maturation and division of megakaryocyte to form functional platelet. The efficacy and safety of the TPO receptor agonists eltrombopag and romiplostim in the treatment of thrombocytopenia in low/intermediate risk-1 MDS patients have been successfully confirmed in foreign studies. Hetrombopag is a new kind of a TPO receptor agonists which is highly specific platelet stimulating factor. At present, there is no large report on the application of Hetrombopag in such patients. The purpose of this study is to explore the short-term and long-term therapeutic effect and safety of Hetrombopag on low/intermediate risk-1 MDS patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: December 1, 2023
• Est. primary completion date: October 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Confirmed MDS, IPSS low / intermediate risk-1

2. In the 4 weeks before inclusion, the average value of platelets was = 30 × 10e9 / L, or < 50 × 10e9 / L with bleeding events

3. Patients with EPO due to anemia and G-CSF due to severe neutropenia can be included, and the dosage will not change during trial

4. ECOG 0-2 points

5. Able to sign informed consent

Exclusion Criteria:

1. Pregnant or lactating

2. IPSS intermediate risk-2 / high risk MDS

3. More than 5% of myeloblasts in bone marrow

4. Myelofibrosis

5. Previous transplantation or ATG treatment within 6 months

6. Previous use of TPO or other TPO receptor agonists

7. Active infection or tumor

8. Thromboembolic or hemorrhagic disease

9. Serious heart disease, including unstable angina, congestive heart failure, arrhythmia, 1-year history of myocardial infarction

10. Baseline liver and kidney function: ALT / ASL over than 3 times normal upper limit, TBIL over than 2 times normal upper limit, and creatinine over than 2 times normal upper limit

Related Conditions & MeSH terms

• MDS
• Thrombocytopenia

Intervention

Drug:
• Hetrombopag
Hetrombopag would be given started with 5mg/day and increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L, the maximum dosage is 15mg/day)
• Stanozolol Tablets
Stanozolol would be given 2mg tid.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (1)

Mei H, Liu X, Li Y, Zhou H, Feng Y, Gao G, Cheng P, Huang R, Yang L, Hu J, Hou M, Yao Y, Liu L, Wang Y, Wu D, Zhang L, Zheng C, Shen X, Hu Q, Liu J, Jin J, Luo J, Zeng Y, Gao S, Zhang X, Zhou X, Shi Q, Xia R, Xie X, Jiang Z, Gao L, Bai Y, Li Y, Xiong J, Li R, Zou J, Niu T, Yang R, Hu Y. A multicenter, randomized phase III trial of hetrombopag: a novel thrombopoietin receptor agonist for the treatment of immune thrombocytopenia. J Hematol Oncol. 2021 Feb 25;14(1):37. doi: 10.1186/s13045-021-01047-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall response rate at 6 months	Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at 6 months	6 month
Secondary	percentage of side effects at 12 months	percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 12 months	12 months
Secondary	ISTH-BAT (ISTH bleeding assessment tool)	to evaluate the severity of bleeding, the proposed normal cutoffs are >=4 in adult males, >=6 in adult females, and >=3 in children, respectively	12 months
Secondary	change of platelet transfusion	the total amount of platelet transfusion per month	12 months
Secondary	onset time for overall response	onset time for complete and partial response	through study completion, an average of 1 year
Secondary	duration of overall response	during time for complete and partial response	through study completion, an average of 1 year
Secondary	life quality for MDS patients	life quality for MDS patients by QoL-E questionaire(scores range from 0 to 100,higher scores mean better).	12 months
Secondary	the change of myeloblasts in bone marrow and peripheral blood	the increased number of myeloblasts in bone marrow and peripheral blood	12 months
Secondary	incidence of progression to high-risk MDS or leukemia	incidence of progression to high-risk MDS or leukemia	12 months