Outcomes in Bone Marrow Aplasia.

NCT ID: NCT06493981

Last Updated: 2024-07-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-31
• Study Completion Date: 2030-07-31

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.

Conditions

Aplastic Anemia Idiopathic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cases of aplastic anemia recieving Eltrombopag

Newely diagnosed bone marrow aplasia starting treatment with Eltrombopag in adose of 50-150mg / day

Group Type: EXPERIMENTAL

Eltrombopag

Intervention Type: DRUG

Treatment with eltrombopag in a dose of (50-150mg/d)

Interventions

Eltrombopag

Treatment with eltrombopag in a dose of (50-150mg/d)

Intervention Type: DRUG

Other Intervention Names

Revolade; Versapenia

Eligibility Criteria

Inclusion Criteria

• Age > 18. Newely diagnosed bone marrow aplasia Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients started CSA plus Eltrombopag therapy Normal cardiac, hepatic & renal functions

Exclusion Criteria

Hypersensitivity or contraindications to eltrombopag. Cardiovascular, pulmonary, hepatic, or renal diseases. History of malignancy. Pregnant, breastfeeding. Inherited bone marrow aplasia. Secondry bone marrow aplasia Previous thromboembolic events. Previous malignancies either solid or hematologic.

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• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Noha Mahmoud

Long term outcomes of eltrombopag in patients with bone marrow aplasia, Assiut university hospital insight.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

Noha Mahmoud Muhammed

Identifier Type: -

Identifier Source: org_study_id