Ignite Creation Date:
2024-07-17 @ 11:43 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06493981
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-10
First Post:
2024-07-02
Brief Title:
Outcomes in Bone Marrow Aplasia
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
Long Term Outcomes of Eltrombopag in Patients With Bone Marrow Aplasia Assiut University Hospital Insight
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Bone marrow aplasia also known as aplastic anemia AA is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells HSCs and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space Underlying mechanisms include immune-mediated attack telomere defects and inherent HSC compartment insufficiency These events may occur individually or in concert mostly involving effector T cells Historical treatment has included the use of high-dose chemotherapy and allogeneic stem cell transplantation as well as lymphotoxic immunosuppressive therapy IST Thrombopoietin TPO regulates platelet production maturation and release through binding of c-mpl on megakaryocytes
Detailed Description:
Eltrombopag E-PAG is an oral synthetic small-molecule noncompetitive TPO agonist that initially was approved by the US Food and Drug Administration FDA for the treatment of chronic immune thrombocytopenic purpura Single-agent activity of E-PAG was demonstrated in at least 1 lineage in 40 to 45 of patients with AA that was refractory to IST leading to its approval by the FDA in this setting 5
Eltrombopag evades cytokines blockade of c-MPL signaling and activates the c-MPL receptor by interacting with the transmembrane receptor domain resulting in a conformational change without competing with TPO Regarding AA it is possible that eltrombopag promotes DNA repair in hematopoietic stem cells and progenitor cells However AA may appear to evolve to other hematologic diseases most notably paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome even to acute myeloid leukemia and about 15 of patients evolve to myelodysplastic syndrome acute myeloid leukemia or both after immunosuppressive therapy Therefore it is unclear but alarming that the use of eltrombopag exacerbates the clone evolution 6
Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia with no unexpected safety concerns This approach might be beneficial where horse-ATG is not available or not tolerated
Eltrombopag evades cytokines blockade of c-MPL signaling and activates the c-MPL receptor by interacting with the transmembrane receptor domain resulting in a conformational change without competing with TPO Regarding AA it is possible that eltrombopag promotes DNA repair in hematopoietic stem cells and progenitor cells However AA may appear to evolve to other hematologic diseases most notably paroxysmal nocturnal hemoglobinuria and myelodysplastic syndrome even to acute myeloid leukemia and about 15 of patients evolve to myelodysplastic syndrome acute myeloid leukemia or both after immunosuppressive therapy Therefore it is unclear but alarming that the use of eltrombopag exacerbates the clone evolution 6
Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia with no unexpected safety concerns This approach might be beneficial where horse-ATG is not available or not tolerated
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None