MDS
Conditions
Brief 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.
Interventions
DRUGHetrombopag
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)
DRUGStanozolol Tablets
Stanozolol would be given 2mg tid.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response rate at 6 months | 6 month | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| percentage of side effects at 12 months | 12 months | percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 12 months |
| ISTH-BAT (ISTH bleeding assessment tool) | 12 months | to evaluate the severity of bleeding, the proposed normal cutoffs are \>=4 in adult males, \>=6 in adult females, and \>=3 in children, respectively |
| change of platelet transfusion | 12 months | the total amount of platelet transfusion per month |
| life quality for MDS patients | 12 months | life quality for MDS patients by QoL-E questionaire（scores range from 0 to 100，higher scores mean better). |
| duration of overall response | through study completion, an average of 1 year | during time for complete and partial response |
| the change of myeloblasts in bone marrow and peripheral blood | 12 months | the increased number of myeloblasts in bone marrow and peripheral blood |
| incidence of progression to high-risk MDS or leukemia | 12 months | incidence of progression to high-risk MDS or leukemia |
| onset time for overall response | through study completion, an average of 1 year | onset time for complete and partial response |
Countries
China
Contacts
Primary ContactBing Han, Docter
Outcome results
None listed