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

A Randomized Trial of Recombinant Human Thrombopoietin Versus Placebo for Low/Intermediate-1 Risk Myelodysplastic Syndromes 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. 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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 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. 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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	Drug: 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
Placebo Comparator: control; Danazol 0.2g tid po+ control (sodium chloride)×14d si every month, total course 6 months	Drug: Danazol + sodium chloride; Danazol 0.2g tid po+ control (sodium chloride)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response rate	overall response rate of platelet	1 year
rate of side effects	rate of all kinds of side effects	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
WHO bleeding score	to evaluate frequency and severity of bleeding	1 year
change of platelet transfusion	the frequency and amount of platelet transfusion	1 year
incidence of TPO antibody	rate of presence of TPO antibody	1 year
life quality for MDS patients	life quality for MDS patients by QoL-E questionaire	1 year
the increased number of myeloblasts in bone marrow and peripheral blood	the increased number of myeloblasts in bone marrow and peripheral blood	1 year
incidence of progression to high-risk MDS or leukemia	incidence of progression to high-risk MDS or leukemia	1 year

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: March 25, 2020
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 26, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: TPO

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