Low/Intermediate Risk-1 MDSPhase 2/3NCT04324060
A Randomized Trial of rhTPO Versus Placebo for Low/Intermediate-1 Risk MDS With Thrombocytopenia
A Phase 2/3 study testing Danazol + rhTPO (recombinant human thrombopoietin injection) and Danazol + sodium chloride in people with Low/Intermediate Risk-1 MDS, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low/Intermediate Risk-1 MDS
- What is being tested?
- Danazol + rhTPO (recombinant human thrombopoietin injection) and Danazol + sodium chloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2020to 1 Dec 2022
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed MDS, IPSS low / intermediate risk-1
- In the 4 weeks before inclusion, the average value of platelets was ≤ 30 × 10e9 / L, or < 50 × 10e9 / L with bleeding events
- Patients with EPO due to anemia and G-CSF due to severe neutropenia can be included, and the dosage will not change during trial
- 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
- ECOG 0-2 points
- Able to sign informed consent
Who cannot join
- Pregnant or lactating
- IPSS intermediate risk-2 / high risk MDS
- More than 5% of myeloblasts in bone marrow
- Myelofibrosis
- Previous transplantation or ATG treatment within 6 months
- Previous use of IL-11, TPO or other TPO receptor agonists
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- Active infection or tumor
- Thromboembolic or hemorrhagic disease
- Serious heart disease, including unstable angina, congestive heart failure, arrhythmia, 1-year history of myocardial infarction
- Intracranial hemorrhage within 4 weeks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Low/Intermediate Risk-1 MDS
- Being tested
- Danazol + rhTPO (recombinant human thrombopoietin injection), Danazol + sodium chloride
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Danazol + rhTPO (recombinant human thrombopoietin injection)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
Danazol + sodium chlorideDrug
Danazol 0.2g tid po+ control (sodium chloride)
| Study group | Role | What they receive |
|---|---|---|
| TPO treatment group | Active comparator | 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 Receives: Drug: Danazol + rhTPO (recombinant human thrombopoietin injection) |
| control | Placebo comparator | Danazol 0.2g tid po+ control (sodium chloride)×14d si every month, total course 6 months Receives: Drug: Danazol + sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall response rate
overall response rate of platelet
Measured: 1 year
rate of side effects
rate of all kinds of side effects
Measured: 1 year
Secondary outcomes (8)
WHO bleeding score
to evaluate frequency and severity of bleeding
Measured: 1 year
change of platelet transfusion
the frequency and amount of platelet transfusion
Measured: 1 year
onset time for overall response
onset time for complete and partial response
Measured: through study completion, an average of 1 year
duration of overall response
during time for complete and partial response
Measured: through study completion, an average of 1 year
incidence of TPO antibody
rate of presence of TPO antibody
Measured: 1 year
life quality for MDS patients
life quality for MDS patients by QoL-E questionaire
Measured: 1 year
the increased number of myeloblasts in bone marrow and peripheral blood
the increased number of myeloblasts in bone marrow and peripheral blood
Measured: 1 year
incidence of progression to high-risk MDS or leukemia
incidence of progression to high-risk MDS or leukemia
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start1 Mar 2020
- Primary completion1 Mar 2022 (estimated)
- Study completion1 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Low/Intermediate Risk-1 MDSStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Bing Han, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04324060
- Sponsor's protocol ID
- TPO
- Status last verified
- Mar 2020
- First submitted
- 25 Mar 2020
- Last updated
- 27 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: protocol, consent form, clinical data would be available by personal contact
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.
PubMed 34778037
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Trial of Recombinant Human Thrombopoietin Versus Placebo for Low/Intermediate-1 Risk Myelodysplastic Syndromes With Thrombocytopenia
- ClinicalTrials.gov ID
- NCT04324060
- Acronym / sponsor ID
- TPO
- Conditions
- Low/Intermediate Risk-1 MDS
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Mar 2020 (actual)
- Primary completion
- 1 Mar 2022 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 27 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TPO treatment group | Active comparator | Drug: 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 |
| control | Placebo comparator | Drug: Danazol + sodium chlorideDanazol 0.2g tid po+ control (sodium chloride)×14d si every month, total course 6 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed MDS, IPSS low / intermediate risk-1
- In the 4 weeks before inclusion, the average value of platelets was ≤ 30 × 10e9 / L, or < 50 × 10e9 / L with bleeding events
- Patients with EPO due to anemia and G-CSF due to severe neutropenia can be included, and the dosage will not change during trial
- 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
- ECOG 0-2 points
Key exclusion criteria (10 listed)
- Pregnant or lactating
- IPSS intermediate risk-2 / high risk MDS
- More than 5% of myeloblasts in bone marrow
- Myelofibrosis
- Previous transplantation or ATG treatment within 6 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Drug | TPO treatment group |
| Danazol + sodium chlorideDanazol 0.2g tid po+ control (sodium chloride) | Drug | control |
Primary outcome
overall response rate
Time frame: 1 year
overall response rate of platelet
rate of side effects
Time frame: 1 year
rate of all kinds of side effects
8 secondary outcomes
WHO bleeding score
Time frame: 1 year
change of platelet transfusion
Time frame: 1 year
onset time for overall response
Time frame: through study completion, an average of 1 year
duration of overall response
Time frame: through study completion, an average of 1 year
incidence of TPO antibody
Time frame: 1 year
life quality for MDS patients
Time frame: 1 year
the increased number of myeloblasts in bone marrow and peripheral blood
Time frame: 1 year
incidence of progression to high-risk MDS or leukemia
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Derived from this study: PubMed 34778037Yang 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.
- Individual participant dataSharing planned: Yes. protocol, consent form, clinical data would be available by personal contact
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Danazol + rhTPO (recombinant human thrombopoietin injection) and Danazol + sodium chloride in people with Low/Intermediate Risk-1 MDS, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall response rate (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04324060, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2020.