Outcomes in Bone Marrow Aplasia.

Long Term Outcomes of Eltrombopag in Patients With Bone Marrow Aplasia, Assiut University Hospital Insight.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Aplastic Anemia Idiopathic
• Intervention / Treatment: Drug: Eltrombopag

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.

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cases of aplastic anemia recieving Eltrombopag; Newely diagnosed bone marrow aplasia starting treatment with Eltrombopag in adose of 50-150mg / day	Drug: Eltrombopag; Treatment with eltrombopag in a dose of (50-150mg/d); Other Names: Revolade; Versapenia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine hematological response after 6 months	Change in CBC elements after 6 months of treatment	6 months to 5 years
Determine overall survival rate.	Number if years estimated to survive after treatment	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of relapse in patients deemed responsers at 6 months.	Around 1 year
Clonal evolution to myeloid malignancy or new chromosomal abnormality	Around 2 years
Change in serum iron and ferritin over time of treatment	From 6 months to 5 years
Eltrombopag efficacy in increasing platelet count	After6 months
Adverse effects raelated to treatment	Within 2 years

Collaborators and Investigators

• Sponsor: Assiut University

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2030

Study Registration Dates

• First Submitted: July 2, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Anemia; Bone Marrow Failure Disorders; Anemia, Aplastic
• Other Study ID Numbers: Noha Mahmoud Muhammed

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No