Clinical trial NCT04324060: A Randomized Trial of rhTPO Versus Placebo for Low/Intermediate-1 Risk MDS With Thrombocytopenia
Official title: A Randomized Trial of Recombinant Human Thrombopoietin Versus Placebo for Low/Intermediate-1 Risk Myelodysplastic Syndromes With Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Low/Intermediate Risk-1 MDS
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
First posted: 2020-03-27
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: overall response rate
timeFrame: 1 year
measure: rate of side effects
timeFrame: 1 year
Secondary outcomes:
measure: WHO bleeding score
timeFrame: 1 year
measure: change of platelet transfusion
timeFrame: 1 year
measure: onset time for overall response
timeFrame: through study completion, an average of 1 year
measure: duration of overall response
timeFrame: through study completion, an average of 1 year
measure: incidence of TPO antibody
timeFrame: 1 year
measure: life quality for MDS patients
timeFrame: 1 year
measure: the increased number of myeloblasts in bone marrow and peripheral blood
timeFrame: 1 year
measure: incidence of progression to high-risk MDS or leukemia
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking union medical college hospital
Study officials:
References:
citation: 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.