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

NCT ID: NCT04324060

Last Updated: 2020-03-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-01
• Study Completion Date: 2022-12-01

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.

Conditions

Low/Intermediate Risk-1 MDS

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

TPO treatment group

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

Group Type: ACTIVE_COMPARATOR

Danazol + rhTPO (recombinant human thrombopoietin injection)

Intervention Type: DRUG

subcutaneous injection, 300U/kg/d×14d every month，stop if the PLT≥100×10e9/L or increased \>50×10e9/L, total course is 6 months

control

Danazol 0.2g tid po+ control (sodium chloride)×14d si every month, total course 6 months

Group Type: PLACEBO_COMPARATOR

Danazol + sodium chloride

Intervention Type: DRUG

Danazol 0.2g tid po+ control (sodium chloride)

Interventions

Danazol + rhTPO (recombinant human thrombopoietin injection)

subcutaneous injection, 300U/kg/d×14d every month，stop if the PLT≥100×10e9/L or increased \>50×10e9/L, total course is 6 months

Intervention Type: DRUG

Danazol + sodium chloride

Danazol 0.2g tid po+ control (sodium chloride)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking Union Medical College Hospital

OTHER

Sponsor Role: lead

Responsible Party

Bing Han

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Peking union medical college hospital

Beijing, , China

Countries

China

References

Yang Y, Tang Z, Ji J, Yang C, Chen M, Han B. Recombinant Human Thrombopoietin Accelerates the Recovery of Platelet in Patients With Lower-Risk Myelodysplastic Syndrome: A Proof-of-Concept Study. Front Oncol. 2021 Oct 28;11:721764. doi: 10.3389/fonc.2021.721764. eCollection 2021.

Reference Type: DERIVED

PMID: 34778037 (View on PubMed)

Other Identifiers

TPO

Identifier Type: -

Identifier Source: org_study_id