Poor Graft FunctionPhase 2NCT03437603
Eltrombopag For Secondary Poor Graft Function Post Allogeneic Hematopoietic Stem Cell Transplantation
A Phase 2 study testing Eltrombopag in people with Poor Graft Function, run by The First Affiliated Hospital of Soochow University at 1 site in China.
Trial summary
To investigate the efficacy and safety for secondary poor graft function (PGF) post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective is the hematologic response rate. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Poor Graft Function
- What is being tested?
- Eltrombopag
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Feb 2018to Jan 2020
- Phase
- Phase 2
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Patients develop poor graft function post allo-HSCT(primary or secondary),who had no response or were transfusion dependent after clinical therapeutic approaches(including growth factors,MSC transfusion,Cluster of differentiation(CD34) positive selected tem cell boosts infusion et al)
- No recurrence or progression of primary malignancy after allo- HSCT
- Patients with full donor chimerism
- Patients without severe GVHD or active infectious diseases, or drug-related myelosuppression;
- Written informed consent obtained from the subject.
Who cannot join
- Alanine aminotransferase(ALT)≥2.5 times the upper limit of normal(ULN)
- Serum bilirubin >2mg/dl
- History of hepatic cirrhosis or the history of portal hypertension
- Patients had any history of arterial / venous thrombosis within 1 year before enrollment in the study.
- Take another treatment for drugs in 30 days or five half-life (no matter which longer) before the first drug delivery.
- Eastern Cooperative Oncology Group(ECOG) performance status≥2.
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- Patients with a birth plan within 1 years, the pregnant or lactating women.
- History of heart disease in the last 3 months, including congestive heart failure(III/IV Level, NHYA) ,arrhythmia, or myocardial infarction which medication is necessary. Any arrhythmia which could increase the risk of thrombotic events, or extended QT interval (QTc) of >480 milliseconds after correction.
- Patients with cataract history；
- Patients with myelofibrosis;
- Patients who are unable to comply in the test and / or follow up stage.
- Any abnormal situation in the screening stage or any other medical history or status that the researchers think is not suitable for the study.
Trial locations and contacts
1 site in 1 country.
China1 site
the First Affiliated Hospital of Soochow University
Suzhou, Jiangsu
Xiaowen Tang, MD, 8613913538266, tangxiaowen@suda.edu.cn
About this study
Official title: A Prospective Single-arm Study to Assess Efficacy and Safety of Eltrombopag For Secondary Poor Graft Function Post Allogeneic Hematopoietic Stem Cell Transplantation
To investigate the efficacy and safety for secondary poor graft function (PGF) post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective is the hematologic response rate. Secondary objectives include: (1) incidence and severity of adverse events; (2) overall survival (OS), and disease-free survival(DFS).
Read the detailed description
Poor graft function (PGF) remains a life-threatening complication that occurs in 5-27% of patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is associated with morbidity and mortality related to infections or hemorrhagic complications.
PGF is defined below: (1) with two or three cytopenic lines (hemoglobin ≤70 g/L, neutrophil count ≤0.5×109/L, platelet count ≤20×109/L) with transfusion requirements; (2) with hypoplastic bone marrow and full donor chimerism; (3) without relapse or severe graft versus host diseases(GVHD) or active infectious diseases, or drug-related myelosuppression; (4) last at least for 14 conductive days. Primary PGF refers to those who did not achieve hematopoietic engraftment at day +28 post-transplant, while secondary PGF(sPGF)was defined as PGF after full engraftment.The underlying pathogenesis of PGF remains unclear. Therapeutic approaches for PGF include (1) growth factors, including granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO)- stimulating factors and thrombopoietin(TPO) mimetics; (2) second allo-HSCT; (3) infusion of additional mobilized cells from the original donor (modified DLI); (4) Cluster of differentiation 34（CD34）positive selected and T cell-depleted stem cell boost(SCB) without conditioning. and (5) mesenchymal stem cell(MSC) transfusion. However, second allo-HSCT and infusion of additional unmanipulated stem cells are associated with high rate of GVHD and treatment-related mortality (TRM). Up to now, there is no standard treatment recommended for PGF patients.
Eltrombopag is a kind of thrombopoietin receptor (TPO-R) agonists which can act as a stimulator of bone marrow progenitor cells.It has been approved by FDA for the treatment of immune thrombocytopenic purpura (ITP) and by European Union for severe aplasia anemia (SAA). Furthermore, there are also increasing amount of clinical trials using Eltrombopag for the treatment of thrombocytopenia post HSCT and very severe aplasia anemia(VSAA) which already had promising results. Due to the similarity in symptoms of PGF and AA, we suggested that if eltrombopag could be beneficial in patients with sPGF post allo-HSCT.
In this single-center open study,20 cases with sPGF post- transplant will be enrolled.The starting dose will be 25mg daily for 3 days to see if the drug is tolerable and then increasing to 50mg for another week. Maintenance dosage is 50mg or 75 mg per day dependent on patients' status and doctors' opinion.Patients may stop medicine when they achieve persistent complete response for 2 weeks.If patients only get partial response or no response after 8 weeks of therapy they may either stop eltrombopag or continue the drug considering doctor's advice. Once a patient suffer severe adverse events,patients should discontinue the drug immediately and get supporting measures.
- Conditions
- Poor Graft Function
- Being tested
- Eltrombopag
- Keywords
- Eltrombopag, Allogenetic Hematopoietic Stem Cell Transplantation, Poor Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Also called Revolade
Starting Eltrombopag daily on empty stomach (2 hour before breakfast) for 8 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Eltrombopag group | Experimental | Starting dose is 25mg daily for the first 3 days, then increasing to 50mg for another week. Maintenance dosage is 50mg or 75 mg per day dependent on patients' status and doctors' opinion.Planned duration of treatment with eltrombopag is 8 weeks.When patients achieve persistent complete response for 2 weeks,they may stop medicine. Receives: Drug: Eltrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate(Complete Response+Partial Response)
Complete Response(CR)：CR was defined as neutrophil count ≥ 1.0×109/L independent of G-CSF for 3 consecutive days;platelets count ≥ 50×109/L without the need of platelet transfusion for at least 7 consecutive days;hemoglobin ≥ 90g/L.
Partial response (PR)：Patients with at least 2 lines of blood cell count meeting the criteria of hematopoietic engraftment but not that of CR were defined as PR.
Measured: 8weeks
Secondary outcomes (5)
Overall Survival(OS)/Disease Free Survival(DFS)
the survival rate after one year from study entry
Measured: 12 months from study entry
Time to complete response
time when a patient achieve complete response
Measured: 8 weeks
Time to achieve each lineage recovery
time to achieve neutrophil/platelet/hemoglobin recovery respectively
Measured: 8weeks
Maintenance time after drug withdrawal
the recurrence time of poor graft function after drug withdrawal
Measured: 12 months from study entry
Incidence of Adverse Events
Safety profile Incidence of Adverse Events according to NCI Common Terminology Criteria for Adverse Events v 4.0 [NCI CTCAE] toxicity scale.
Measured: 12months from study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study startFeb 2018 (estimated)
- Primary completionJan 2019 (estimated)
- Study completionJan 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Poor Graft FunctionStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The First Affiliated Hospital of Soochow University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Xiaowen Tang, The First Affiliated Hospital of Soochow University
- Investigators
- Xiaowen Tang, MD, Principal investigator, The First Affliated Hospital of Soochow University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437603
- Sponsor's protocol ID
- Eltrombopag For PGF
- Status last verified
- Feb 2018
- First submitted
- 27 Jan 2018
- Last updated
- 19 Feb 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Single-arm Study to Assess Efficacy and Safety of Eltrombopag For Secondary Poor Graft Function Post Allogeneic Hematopoietic Stem Cell Transplantation
- ClinicalTrials.gov ID
- NCT03437603
- Acronym / sponsor ID
- Eltrombopag For PGF
- Conditions
- Poor Graft Function
- Keywords
- Eltrombopag, Allogenetic Hematopoietic Stem Cell Transplantation, Poor Graft Function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital of Soochow UniversityUniversity, hospital or other
- Study start
- Feb 2018 (estimated)
- Primary completion
- Jan 2019 (estimated)
- Study completion
- Jan 2020 (estimated)
- First posted
- 19 Feb 2018 (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.
To investigate the efficacy and safety for secondary poor graft function (PGF) post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective is the hematologic response rate. Secondary objectives include: (1) incidence and severity of adverse events; (2) overall survival (OS), and disease-free survival(DFS).
Detailed description
Poor graft function (PGF) remains a life-threatening complication that occurs in 5-27% of patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is associated with morbidity and mortality related to infections or hemorrhagic complications.
PGF is defined below: (1) with two or three cytopenic lines (hemoglobin ≤70 g/L, neutrophil count ≤0.5×109/L, platelet count ≤20×109/L) with transfusion requirements; (2) with hypoplastic bone marrow and full donor chimerism; (3) without relapse or severe graft versus host diseases(GVHD) or active infectious diseases, or drug-related myelosuppression; (4) last at least for 14 conductive days. Primary PGF refers to those who did not achieve hematopoietic engraftment at day +28 post-transplant, while secondary PGF(sPGF)was defined as PGF after full engraftment.The underlying pathogenesis of PGF remains unclear. Therapeutic approaches for PGF include (1) growth factors, including granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO)- stimulating factors and thrombopoietin(TPO) mimetics; (2) second allo-HSCT; (3) infusion of additional mobilized cells from the original donor (modified DLI); (4) Cluster of differentiation 34（CD34）positive selected and T cell-depleted stem cell boost(SCB) without conditioning. and (5) mesenchymal stem cell(MSC) transfusion. However, second allo-HSCT and infusion of additional unmanipulated stem cells are associated with high rate of GVHD and treatment-related mortality (TRM). Up to now, there is no standard treatment recommended for PGF patients.
Eltrombopag is a kind of thrombopoietin receptor (TPO-R) agonists which can act as a stimulator of bone marrow progenitor cells.It has been approved by FDA for the treatment of immune thrombocytopenic purpura (ITP) and by European Union for severe aplasia anemia (SAA). Furthermore, there are also increasing amount of clinical trials using Eltrombopag for the treatment of thrombocytopenia post HSCT and very severe aplasia anemia(VSAA) which already had promising results. Due to the similarity in symptoms of PGF and AA, we suggested that if eltrombopag could be beneficial in patients with sPGF post allo-HSCT.
In this single-center open study,20 cases with sPGF post- transplant will be enrolled.The starting dose will be 25mg daily for 3 days to see if the drug is tolerable and then increasing to 50mg for another week. Maintenance dosage is 50mg or 75 mg per day dependent on patients' status and doctors' opinion.Patients may stop medicine when they achieve persistent complete response for 2 weeks.If patients only get partial response or no response after 8 weeks of therapy they may either stop eltrombopag or continue the drug considering doctor's advice. Once a patient suffer severe adverse events,patients should discontinue the drug immediately and get supporting measures.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eltrombopag group | Experimental | Drug: EltrombopagStarting dose is 25mg daily for the first 3 days, then increasing to 50mg for another week. Maintenance dosage is 50mg or 75 mg per day dependent on patients' status and doctors' opinion.Planned duration of treatment with eltrombopag is 8 weeks.When patients achieve persistent complete response for 2 weeks,they may stop medicine. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Patients develop poor graft function post allo-HSCT(primary or secondary),who had no response or were transfusion dependent after clinical therapeutic approaches(including growth factors,MSC transfusion,Cluster of differentiation(CD34) positive selected tem cell boosts infusion et al)
- No recurrence or progression of primary malignancy after allo- HSCT
- Patients with full donor chimerism
- Patients without severe GVHD or active infectious diseases, or drug-related myelosuppression;
- Written informed consent obtained from the subject.
Key exclusion criteria (12 listed)
- Alanine aminotransferase(ALT)≥2.5 times the upper limit of normal(ULN)
- Serum bilirubin >2mg/dl
- History of hepatic cirrhosis or the history of portal hypertension
- Patients had any history of arterial / venous thrombosis within 1 year before enrollment in the study.
- Take another treatment for drugs in 30 days or five half-life (no matter which longer) before the first drug delivery.
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 |
|---|---|---|
| EltrombopagAlso: RevoladeStarting Eltrombopag daily on empty stomach (2 hour before breakfast) for 8 weeks. | Drug | Eltrombopag group |
Primary outcome
Overall Response Rate(Complete Response+Partial Response)
Time frame: 8weeks
Complete Response(CR)：CR was defined as neutrophil count ≥ 1.0×109/L independent of G-CSF for 3 consecutive days;platelets count ≥ 50×109/L without the need of platelet transfusion for at least 7 consecutive days;hemoglobin ≥ 90g/L. Partial response (PR)：Patients with at least 2 lines of blood cell count meeting the criteria of hematopoietic engraftment but not that of CR were defined as PR.
5 secondary outcomes
Overall Survival(OS)/Disease Free Survival(DFS)
Time frame: 12 months from study entry
Time to complete response
Time frame: 8 weeks
Time to achieve each lineage recovery
Time frame: 8weeks
Maintenance time after drug withdrawal
Time frame: 12 months from study entry
Incidence of Adverse Events
Time frame: 12months from study entry
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2018.
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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.
Xiaowen Tang, MD principal investigator
The First Affliated Hospital of Soochow University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Eltrombopag in people with Poor Graft Function, run by The First Affiliated Hospital of Soochow University 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 5 inclusion and 12 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 19 Feb 2018. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
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?
Contact Xiaowen Tang, MD (8613913538266, tangxiaowen@suda.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate(Complete Response+Partial Response) (time frame: 8weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Feb 2018.