Hetrombopag for Low/Intermediate-1 Risk MDS With Thrombocytopenia

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: MDS
• Intervention / Treatment: Drug: Hetrombopag; Drug: Stanozolol Tablets

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Bing Han, Docter; Phone Number: +8613601059938; Email: hanbing_li@sina.com

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Hetrombopag treatment group; stanozolol 2mg tid + Hetrombopag (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)	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); Drug: Stanozolol Tablets; Stanozolol would be given 2mg tid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
change of platelet transfusion	the total amount of platelet transfusion per month	12 months
onset time for overall response	onset time for complete and partial response	through study completion, an average of 1 year
duration of overall response	during time for complete and partial response	through study completion, an average of 1 year
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
the change of myeloblasts in bone marrow and peripheral blood	the increased number of myeloblasts in bone marrow and peripheral blood	12 months
incidence of progression to high-risk MDS or leukemia	incidence of progression to high-risk MDS or leukemia	12 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Bing Han, Docter, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: August 19, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 27, 2021

Study Record Updates

• Last Update Posted (Actual): September 24, 2021
• Last Update Submitted That Met QC Criteria: September 18, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Anabolic Agents; Stanozolol
• Other Study ID Numbers: HBP-MDS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: protocol, consent form, clinical data would be available by personal contact
• IPD Sharing Time Frame: 10 years
• IPD Sharing Access Criteria: personal contact including emails
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

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