EltrombopagPhase 4EltroplasticNCT03243656
Eltrombopag & Cyclosporine in Children With Sever Aplastic Anemia
A Phase 4 study testing Eltrombopag in people with Eltrombopag, run by Assiut University at 1 site in Egypt.
Trial summary
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality. Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell… Read more about this study
- Who is it for?
- Ages 1 year to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Eltrombopag
- What is being tested?
- Eltrombopag
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteEgypt
- Study dates
- 20 Dec 2017to 5 Jan 2020
- Phase
- Phase 4
- 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 1 year to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Current diagnosis of sever Aplastic anemia
- Diagnosis of sever Aplastic anemia is established if Bone marrow cellularity <25% or and at least two of the following criteria are met:- (i) absolute neutrophil count less than 0.5 × 109/L, (ii) platelet count less than 20 × 109/L, and (iii) reticulocyte count less than 20 × 109/L
- No, evidence of viral or drug suppression of the marrow, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
- Age equal to 1 years old to 18 years old
- Written informed consent signed by a parent or legal guardian prior to initiation of any study specific procedure.
- Hematopoietic stem cell transplantation is not available or suitable as a treatment option or has been refused by the patient.
- Bone marrow aspirate and biopsy at any time during the 4 weeks prior to first dose of eltrombopag
Who cannot join
- Prior and/or active medical history of:-
- Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry). Other known underlying congenital/inherited marrow failure syndromes.
- Symptomatic Paroxysmal Nocturnal Hemoglobinuria
- Other known or suspected underlying primary immunodeficiency
- Any malignancy
- Active infection not responding to appropriate therapy
Show all 9Show fewer
- Any out of range lab values Creatinine >2.5 mg/dL× the upper limit of normal, Total bilirubin >1.5 × the upper limit of normal mg/dL ,Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 × the upper limit of normal
- Hypersensitivity to eltrombopag or its components
- Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the patient's ability to tolerate protocol therapy, or that death within 7-10 days is likely.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Clinical Trial of the Use of & Cyclosporine in Children With Sever Idiopathic Aplastic Anemia
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality.
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .
Read the detailed description
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia) . The clinical consequences are anemia, usually with a requirement for frequent red blood cell transfusions, life-threatening bleeding from thrombocytopenia, and infection because of neutropenia. Bacterial and fungal infections are most common and are a significant cause of morbidity and mortality.
The incidence of acquired Aplastic anemia in Europe and North America is around two per million children per year . The incidence is 2-3 times higher in East Asia. There is no significant difference in incidence between males and females .
The pathogenesis of Aplastic anemia is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity disorders. The etiological basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. The distinction between acquired and inherited disease may present a clinical challenge, Congenital or inherited causes of Aplastic anemia are responsible for at least 25% of children with this condition and for perhaps up to 10% of adults. Acquired causes of Aplastic anemia form (80%) of cases, include Idiopathic (> 80 %), Post-infectious 15% (particularly after hepatitis 9%, Epstein-Barr virus , human immune deficiency virus, parvovirus, and mycobacteria, Drug-induced and toxins (4%).
Definitive and potentially curative therapy with haematopoietic stem cell transplantation However, only a minority (30 %) of patients have a suitable donor. Immunosuppressive therapy with horse or rabbit antithymocyte globulin plus cyclosporine is the most commonly used alternative treatment in about two thirds of cases. Response is associated with a favorable long-term outlook. 30 -40% of patients are refractory to immunosuppressive therapy and remain pancytopenic after therapy. Even patients that respond to immunosuppressive therapies with an improvement in their life-threatening neutropenia sometimes have persistent thrombocytopenia .
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
Thrombopoietin is a glycoprotein class 1 hematopoietic cytokine, produced primarily in the liver. It is a critical regulator of hematopoiesis. It acts through the thrombopoietin receptor which is expressed on hematopoietic stem and progenitor cells. Action results in a number of signal transduction events that prevent apoptosis, improve cell viability, promote growth, and possibly increase differentiation.
Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .Eltrombopag became the first oral platelet growth factor to receive Food and Drug Administration approval in 2008. This initial indication was for adult patients with chronic immune thrombocytopenic purpura. In 24 August 2015, this indication was extended to children age 1 to 17 with the same condition. In addition, it has been recently shown to be efficacious in the setting of aplastic anemia with trilineage responses in some patients and many achieving transfusion independence. It has license by the European Medicines Agency for this indication in August 2015. In 2017, the National Institutes of Health made Eltrombopag a standard of care in Aplastic anemia
- Conditions
- Eltrombopag
- Being tested
- Eltrombopag
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EltrombopagDrug
Also called Revolade
An oral thrombopoietin receptor agonist
| Study group | Role | What they receive |
|---|---|---|
| historical group | No intervention | Immunosuppressive therapy (cyclosporine alone ), |
| case arm | Active comparator | cyclosporine plus an oral dose of Eltrombopag Receives: Drug: Eltrombopag |
What is being measured
The primary outcome is the main question the study is designed to answer.
changes in Platelet count (at Baseline, 26 Weeks and up to 52 week)
increase of platelet count from baseline by 20,000/microliter or more (in the absence of platelet transfusion), or independence from platelet transfusions for a minimum of 8 weeks in patients who were previously transfusion-dependent.
Measured: 52 week
Changes in hemoglobin count (at Baseline, 26 Weeks and up to 52 week)
measuring the following: Increase from baseline by 1.5 gram g/dL or more when the baseline hemoglobin level is <8.5 g/dL and no red blood cell (RBC) transfusion at baseline. A decrease of at least four units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period..
Measured: 52 week
changes in absolute Neutrophil count (at Baseline, 26 Weeks and up to 52 week)
measuring the increase in the absolute neutrophil count of more than 500 per cubic millimeter
Measured: 52 week
complete response (CR) - 12 month
CR defined as all three parameters meet the following criteria : Hb ≥100 g/l, platelet count ≥100 × 109/L, and ANC ≥1 × 109/L. Additionally, patients had to be transfusion and growth factor independent
Measured: 52 weeks
Partial response (PR) - 12 month
PR was defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of sever aplastic anemia (SAA): Absolute neutrophil count (ANC) >500/μL Platelet count >20 000/μL Reticulocyte count >20 000/μL
Measured: 52 weeks
Secondary outcomes (6)
The hematological responses
Duration of hematologic response Time from the date of the start of response to the date of relapse defined as again meeting criteria for severe or moderate aplastic anemia Duration of platelet and blood transfusion independence Transfusion independency is defined when blood and platelet transfusions are not required in a consecutive 8-week period. Transfusion dependency will be defined as at least 2 units of red blood cells or five units of random platelets or equivalent apheresis per month for a period of 8 weeks. The duration of platelet and blood transfusion independence will be evaluated separately.
Measured: up to to 52 week
The toxicity
Number of participants with adverse events Measure toxicity, using CTCAE associated with assessment of eltrombopag use, dose, and tolerability in patients with sever to very severe aplastic anemia
Measured: Up to 30 days after last dose of study treatment
complete response (CR)- 6 month
CR defined as all three parameters meet the following criteria : Hb ≥100 g/l, platelet count ≥100 × 109/L, and ANC ≥1 × 109/L. Additionally, patients had to be transfusion and growth factor independent
Measured: 26 week
Partial response (PR) - 6 month
PR was defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of SAA.
Absolute neutrophil count (ANC) >500/μL Platelet count >20 000/μL Reticulocyte count >20 000/μL
Measured: 26 week
Overall hematologic response (CR + PR) rate - 6 month
Overall hematologic response = patients with complete response + patients with partial response .
Partial response is defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of SAA
ANC >500/μL Platelet count >20 000/μL Reticulocyte count >20 000/μL
Complete response is defined as all three parameters meet the following criteria:
ANC > 1 000/μL Platelet count >100 000/μL Hemoglobin >10 g/L
Measured: 26 week
Overall hematologic response (CR + PR) rate - 12 month
Overall hematologic response = patients with complete response + patients with partial response.
Partial response is defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of SAA
ANC >500/μL Platelet count >20 000/μL Reticulocyte count >20 000/μL
Complete response is defined as all three parameters meet the following criteria:
ANC > 1 000/μL Platelet count >100 000/μL Hemoglobin >10 g/L
Measured: 52 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2017
- Study start20 Dec 2017
- Primary completion29 Dec 2019
- Study completion5 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for EltrombopagStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mai Ali Abdelfatah Ahmed, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03243656
- Sponsor's protocol ID
- MAAhmed
- Acronym
- Eltroplastic
- Status last verified
- Jan 2022
- First submitted
- 2 Aug 2017
- Last updated
- 18 Jan 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guinan EC. Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am. 2009 Apr;23(2):171-91. doi: 10.1016/j.hoc.2009.01.011.
PubMed 19327578Young NS, Bacigalupo A, Marsh JC. Aplastic anemia: pathophysiology and treatment. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S119-25. doi: 10.1016/j.bbmt.2009.09.013. Epub 2009 Sep 24.
PubMed 19782144Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS. The epidemiology of aplastic anemia in Thailand. Blood. 2006 Feb 15;107(4):1299-307. doi: 10.1182/blood-2005-01-0161. Epub 2005 Oct 27.
PubMed 16254144Marsh JC, Mufti GJ. Eltrombopag: a stem cell cookie? Blood. 2014 Mar 20;123(12):1774-5. doi: 10.1182/blood-2014-02-553404. No abstract available.
PubMed 24652959Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69(5):567-76. doi: 10.2165/00003495-200969050-00005.
PubMed 19368418Montane E, Ibanez L, Vidal X, Ballarin E, Puig R, Garcia N, Laporte JR; Catalan Group for Study of Agranulocytosis and Aplastic Anemia. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008 Apr;93(4):518-23. doi: 10.3324/haematol.12020. Epub 2008 Mar 5.
PubMed 18322256Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SE. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007 Dec 13;1(6):671-84. doi: 10.1016/j.stem.2007.10.008. Epub 2007 Nov 20.
PubMed 18371408Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood. 2008 Feb 1;111(3):981-6. doi: 10.1182/blood-2007-05-088500.
PubMed 18223171Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275.
PubMed 18046028de Laval B, Pawlikowska P, Petit-Cocault L, Bilhou-Nabera C, Aubin-Houzelstein G, Souyri M, Pouzoulet F, Gaudry M, Porteu F. Thrombopoietin-increased DNA-PK-dependent DNA repair limits hematopoietic stem and progenitor cell mutagenesis in response to DNA damage. Cell Stem Cell. 2013 Jan 3;12(1):37-48. doi: 10.1016/j.stem.2012.10.012. Epub 2012 Dec 13.
PubMed 23246483Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931.
PubMed 22762314Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014 Mar 20;123(12):1818-25. doi: 10.1182/blood-2013-10-534743. Epub 2013 Dec 17.
PubMed 24345753Alter BP. Aplastic Anemia, Pediatric Aspects. Oncologist. 1996;1(6):361-366.
PubMed 10388017Ballmaier M, Germeshausen M, Krukemeier S, Welte K. Thrombopoietin is essential for the maintenance of normal hematopoiesis in humans: development of aplastic anemia in patients with congenital amegakaryocytic thrombocytopenia. Ann N Y Acad Sci. 2003 May;996:17-25. doi: 10.1111/j.1749-6632.2003.tb03228.x.
PubMed 12799278Dezern AE, Brodsky RA. Clinical management of aplastic anemia. Expert Rev Hematol. 2011 Apr;4(2):221-30. doi: 10.1586/ehm.11.11.
PubMed 21495931
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Clinical Trial of the Use of & Cyclosporine in Children With Sever Idiopathic Aplastic Anemia
- ClinicalTrials.gov ID
- NCT03243656
- Acronym / sponsor ID
- Eltroplastic / MAAhmed
- Conditions
- Eltrombopag
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 20 Dec 2017 (actual)
- Primary completion
- 29 Dec 2019 (actual)
- Study completion
- 5 Jan 2020 (actual)
- First posted
- 9 Aug 2017 (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.
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.but,It is very serious disease causing morbidity and mortality.
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .
Detailed description
Aplastic anemia is a rare disorder characterized by pancytopenia and a hypo cellular bone marrow.This causes a deficiency of all three blood cell types (pancytopenia): red blood cells (anemia), white blood cells (leukopenia), and platelets (thrombocytopenia) . The clinical consequences are anemia, usually with a requirement for frequent red blood cell transfusions, life-threatening bleeding from thrombocytopenia, and infection because of neutropenia. Bacterial and fungal infections are most common and are a significant cause of morbidity and mortality.
The incidence of acquired Aplastic anemia in Europe and North America is around two per million children per year . The incidence is 2-3 times higher in East Asia. There is no significant difference in incidence between males and females .
The pathogenesis of Aplastic anemia is complex and involves an abnormal hematopoietic microenvironment, hematopoietic stem cell/progenitor cell deficiencies and immunity disorders. The etiological basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. The distinction between acquired and inherited disease may present a clinical challenge, Congenital or inherited causes of Aplastic anemia are responsible for at least 25% of children with this condition and for perhaps up to 10% of adults. Acquired causes of Aplastic anemia form (80%) of cases, include Idiopathic (> 80 %), Post-infectious 15% (particularly after hepatitis 9%, Epstein-Barr virus , human immune deficiency virus, parvovirus, and mycobacteria, Drug-induced and toxins (4%).
Definitive and potentially curative therapy with haematopoietic stem cell transplantation However, only a minority (30 %) of patients have a suitable donor. Immunosuppressive therapy with horse or rabbit antithymocyte globulin plus cyclosporine is the most commonly used alternative treatment in about two thirds of cases. Response is associated with a favorable long-term outlook. 30 -40% of patients are refractory to immunosuppressive therapy and remain pancytopenic after therapy. Even patients that respond to immunosuppressive therapies with an improvement in their life-threatening neutropenia sometimes have persistent thrombocytopenia .
Aplastic anemia can be treated effectively with haematopoietic stem cell transplantation and immunosuppressive drug regimens but haematopoietic stem cell transplantation has limitations due to its cost and many patient are unsuitable. Immunosuppressive drug has a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload and transfusion.
Thrombopoietin is a glycoprotein class 1 hematopoietic cytokine, produced primarily in the liver. It is a critical regulator of hematopoiesis. It acts through the thrombopoietin receptor which is expressed on hematopoietic stem and progenitor cells. Action results in a number of signal transduction events that prevent apoptosis, improve cell viability, promote growth, and possibly increase differentiation.
Eltrombopag is an oral thrombopoietin mimetic that selectively binds at the transmembrane and juxtamembrane domains of the thrombopoietin receptor, at sites distinct from the binding site of thrombopoietin therefore it does not compete for binding with the native molecule. It promoting thrombopoiesis and release of platelets from mature megakaryocytes. Also, promote other hematopoietic stem cell as well as in thrombopoiesis .Eltrombopag became the first oral platelet growth factor to receive Food and Drug Administration approval in 2008. This initial indication was for adult patients with chronic immune thrombocytopenic purpura. In 24 August 2015, this indication was extended to children age 1 to 17 with the same condition. In addition, it has been recently shown to be efficacious in the setting of aplastic anemia with trilineage responses in some patients and many achieving transfusion independence. It has license by the European Medicines Agency for this indication in August 2015. In 2017, the National Institutes of Health made Eltrombopag a standard of care in Aplastic anemia
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| historical group | No intervention | –Immunosuppressive therapy (cyclosporine alone ), |
| case arm | Active comparator | Drug: Eltrombopagcyclosporine plus an oral dose of Eltrombopag |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Current diagnosis of sever Aplastic anemia
- Diagnosis of sever Aplastic anemia is established if Bone marrow cellularity <25% or and at least two of the following criteria are met:- (i) absolute neutrophil count less than 0.5 × 109/L, (ii) platelet count less than 20 × 109/L, and (iii) reticulocyte count less than 20 × 109/L
- No, evidence of viral or drug suppression of the marrow, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
- Age equal to 1 years old to 18 years old
- Written informed consent signed by a parent or legal guardian prior to initiation of any study specific procedure.
Key exclusion criteria (9 listed)
- Prior and/or active medical history of:-
- Fanconi anemia (via chromosomal breakage test or growth arrest by flow cytometry). Other known underlying congenital/inherited marrow failure syndromes.
- Symptomatic Paroxysmal Nocturnal Hemoglobinuria
- Other known or suspected underlying primary immunodeficiency
- Any malignancy
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: RevoladeAn oral thrombopoietin receptor agonist | Drug | case arm |
Primary outcome
changes in Platelet count (at Baseline, 26 Weeks and up to 52 week)
Time frame: 52 week
increase of platelet count from baseline by 20,000/microliter or more (in the absence of platelet transfusion), or independence from platelet transfusions for a minimum of 8 weeks in patients who were previously transfusion-dependent.
Changes in hemoglobin count (at Baseline, 26 Weeks and up to 52 week)
Time frame: 52 week
measuring the following: Increase from baseline by 1.5 gram g/dL or more when the baseline hemoglobin level is <8.5 g/dL and no red blood cell (RBC) transfusion at baseline. A decrease of at least four units in RBC transfusions in the post-treatment 8-week period compared to the pre-treatment 8-week period..
changes in absolute Neutrophil count (at Baseline, 26 Weeks and up to 52 week)
Time frame: 52 week
measuring the increase in the absolute neutrophil count of more than 500 per cubic millimeter
complete response (CR) - 12 month
Time frame: 52 weeks
CR defined as all three parameters meet the following criteria : Hb ≥100 g/l, platelet count ≥100 × 109/L, and ANC ≥1 × 109/L. Additionally, patients had to be transfusion and growth factor independent
Partial response (PR) - 12 month
Time frame: 52 weeks
PR was defined as blood count no longer meeting Camitta criteria for severs aplastic anemia in case of sever aplastic anemia (SAA): Absolute neutrophil count (ANC) >500/μL Platelet count >20 000/μL Reticulocyte count >20 000/μL
6 secondary outcomes
The hematological responses
Time frame: up to to 52 week
The toxicity
Time frame: Up to 30 days after last dose of study treatment
complete response (CR)- 6 month
Time frame: 26 week
Partial response (PR) - 6 month
Time frame: 26 week
Overall hematologic response (CR + PR) rate - 6 month
Time frame: 26 week
Overall hematologic response (CR + PR) rate - 12 month
Time frame: 52 week
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2022.
- Background: PubMed 19327578Guinan EC. Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am. 2009 Apr;23(2):171-91. doi: 10.1016/j.hoc.2009.01.011.
- Background: PubMed 19782144Young NS, Bacigalupo A, Marsh JC. Aplastic anemia: pathophysiology and treatment. Biol Blood Marrow Transplant. 2010 Jan;16(1 Suppl):S119-25. doi: 10.1016/j.bbmt.2009.09.013. Epub 2009 Sep 24.
- Background: PubMed 16254144Issaragrisil S, Kaufman DW, Anderson T, Chansung K, Leaverton PE, Shapiro S, Young NS. The epidemiology of aplastic anemia in Thailand. Blood. 2006 Feb 15;107(4):1299-307. doi: 10.1182/blood-2005-01-0161. Epub 2005 Oct 27.
- Background: PubMed 24652959Marsh JC, Mufti GJ. Eltrombopag: a stem cell cookie? Blood. 2014 Mar 20;123(12):1774-5. doi: 10.1182/blood-2014-02-553404. No abstract available.
- Background: PubMed 19368418Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69(5):567-76. doi: 10.2165/00003495-200969050-00005.
- Background: PubMed 18322256Montane E, Ibanez L, Vidal X, Ballarin E, Puig R, Garcia N, Laporte JR; Catalan Group for Study of Agranulocytosis and Aplastic Anemia. Epidemiology of aplastic anemia: a prospective multicenter study. Haematologica. 2008 Apr;93(4):518-23. doi: 10.3324/haematol.12020. Epub 2008 Mar 5.
- Background: PubMed 18371408Qian H, Buza-Vidas N, Hyland CD, Jensen CT, Antonchuk J, Mansson R, Thoren LA, Ekblom M, Alexander WS, Jacobsen SE. Critical role of thrombopoietin in maintaining adult quiescent hematopoietic stem cells. Cell Stem Cell. 2007 Dec 13;1(6):671-84. doi: 10.1016/j.stem.2007.10.008. Epub 2007 Nov 20.
- Background: PubMed 18223171Kaushansky K. Historical review: megakaryopoiesis and thrombopoiesis. Blood. 2008 Feb 1;111(3):981-6. doi: 10.1182/blood-2007-05-088500.
- Background: PubMed 18046028Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. doi: 10.1056/NEJMoa073275.
- Background: PubMed 23246483de Laval B, Pawlikowska P, Petit-Cocault L, Bilhou-Nabera C, Aubin-Houzelstein G, Souyri M, Pouzoulet F, Gaudry M, Porteu F. Thrombopoietin-increased DNA-PK-dependent DNA repair limits hematopoietic stem and progenitor cell mutagenesis in response to DNA damage. Cell Stem Cell. 2013 Jan 3;12(1):37-48. doi: 10.1016/j.stem.2012.10.012. Epub 2012 Dec 13.
- Background: PubMed 22762314Olnes MJ, Scheinberg P, Calvo KR, Desmond R, Tang Y, Dumitriu B, Parikh AR, Soto S, Biancotto A, Feng X, Lozier J, Wu CO, Young NS, Dunbar CE. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med. 2012 Jul 5;367(1):11-9. doi: 10.1056/NEJMoa1200931.
- Background: PubMed 24345753Desmond R, Townsley DM, Dumitriu B, Olnes MJ, Scheinberg P, Bevans M, Parikh AR, Broder K, Calvo KR, Wu CO, Young NS, Dunbar CE. Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug. Blood. 2014 Mar 20;123(12):1818-25. doi: 10.1182/blood-2013-10-534743. Epub 2013 Dec 17.
- Individual participant dataSharing planned: No
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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.
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 4 study testing Eltrombopag in people with Eltrombopag, run by Assiut University at 1 site in Egypt.
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 7 inclusion and 9 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: finished, as of the sponsor's last update on 18 Jan 2022. 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 Egypt. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
changes in Platelet count (at Baseline, 26 Weeks and up to 52 week) (time frame: 52 week). The study lists 5 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 NCT03243656, which also lists 24 linked publications.
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 18 Jan 2022.