A Randomized Trial of rhTPO Versus Placebo for Low/Intermediate-1 Risk MDS With Thrombocytopenia

Phase 2

• Conditions: Low/Intermediate Risk-1 MDS
• Interventions: Drug: Danazol + sodium chloride; Drug: Danazol + rhTPO (recombinant human thrombopoietin injection)

• Registration Number: NCT04324060
• Lead Sponsor: Peking Union Medical College Hospital

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. Recombinant human thrombopoietin (rhTPO) is also a kind of a TPO receptor agonists which is highly specific platelet stimulating factor. At present, there is no large report on the application of rhTPO in such patients. The purpose of this study is to explore the short-term and long-term therapeutic effect and safety of rhTPO on low/intermediate risk-1 MDS patients.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-03
• Study Start: 2020-03-01
• Study First Submitted: 2020-03-25
• Study First Submitted QC: 2020-03-26
• Last Update Submitted: 2020-03-26
• Study First Posted: 2020-03-27
• Last Update Posted: 2020-03-27
• Primary Completion: 2022-03-01
• Study Completion: 2022-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

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. Baseline liver and kidney function: ALT / ASL within 3 times normal upper limit, TBIL within 2 times normal upper limit, and creatinine within 2 times normal upper limit
5. ECOG 0-2 points
6. 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 IL-11, 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. Intracranial hemorrhage within 4 weeks

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
control	Danazol + sodium chloride	Danazol 0.2g tid po+ control (sodium chloride)×14d si every month, total course 6 months
TPO treatment group	Danazol + rhTPO (recombinant human thrombopoietin injection)	Danazol 0.2g tid po+rhTPO (recombinant human thrombopoietin injection) 300U/kg/d×14d si every month (stop when PLT≥100×10e9/L or increased more than 50×10e9/L), total course 6 months

Primary Outcome Measures

Name	Time	Method
rate of side effects	1 year	rate of all kinds of side effects
overall response rate	1 year	overall response rate of platelet

Secondary Outcome Measures

Name	Time	Method
incidence of progression to high-risk MDS or leukemia	1 year	incidence of progression to high-risk MDS or leukemia
change of platelet transfusion	1 year	the frequency and amount of platelet transfusion
WHO bleeding score	1 year	to evaluate frequency and severity of bleeding
onset time for overall response	through study completion, an average of 1 year	onset time for complete and partial response
life quality for MDS patients	1 year	life quality for MDS patients by QoL-E questionaire
duration of overall response	through study completion, an average of 1 year	during time for complete and partial response
incidence of TPO antibody	1 year	rate of presence of TPO antibody
the increased number of myeloblasts in bone marrow and peripheral blood	1 year	the increased number of myeloblasts in bone marrow and peripheral blood

Trial Locations

Locations (1)

Peking union medical college hospital; 🇨🇳 Beijing, China