Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia

Study Overview
=================
Brief Summary
-----------------
To the investigator's Knowledge this is the first study that will assess Treatment with thrombopoietin Mimetic plus immunosuppressiveTherapy in Egyptian Patients with Aplastic Anaemia. Aim of the work : To evaluate the efficacy, tolerability and toxicity of the combination of thrombopoietin mimetic and immunosuppressive therapy in Egyptian patients with AA. To study the influence of this combination on patients' quality of life. To access evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome , acute leukemia or development of fibrosis

Detailed Description
-----------------
Aplastic anemia (AA) is a bone marrow failure syndrome that, although benign in nature, it influences patients' quality of life and carries poor prognosis.The pathophysiological basis of development of acquired AA include immune-mediated attack, inherent hematopoietic stem cell insufficiency and telomere defects. Bone marrow transplantation (BMT) is the only curative treatment for AA. Unfortunately it is unavailable for many patients due to lack of matched donors furthermore others are ineligible for BMT due to old age or co-morbid conditions. Immunosuppressive therapy was the mainstay of treatment for AA for many years, however many patients developed resistance or refractoriness. Immunosuppressive therapy was in the form of antithymocyte globulin (ATG) which gave hematologic response in nearly 50% of patients , adding cyclosporin A increases this response to 70%. Why some patients became resistant to immunosuppressive therapy ? The answer is not known. Thrombopoietin mimetic (Eltrombopag) was firstly FDA approved for treatment of immune thrombocytopenic purpura. Numerous clinical trials proved the efficacy of anthropometric mimetic in patients with refractory severe AA, leading to its FDA approval for this group of patients. Some researchers proven the efficacy of thrombopoietin mimetic in patients with moderate aplastic anemia. This study aimed to asses the combination of thrombopoietin mimetic and immunosuppressive therapy in patients with AA.

Official Title
-----------------
Treatment With Thrombopoietin Mimetic Plus Immunosuppressive Therapy in Egyptian Patients With Aplastic Anaemia

Conditions
-----------------
Aplastic Anemia

Intervention / Treatment
-----------------
* Drug: Combination of thrombopoietin mimetic and cyclosporin A


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Eligible for treatment with thrombopoietin mimetic. Willing to participate in the study and signed informed consent. Unavailability of BMT - Exclusion Criteria: Patient with inherited aplastic anemia Underlying immune deficiency Contra indication to cyclosporin A Endstage hepatic or renal disease Pregnancy and lactation

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups of patients will be included one group will be treated with thrombopoietin mimetic and immunosuppressive therapy , another matched group treated with immunosuppressive therapy alone and enrolled retrospectively
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thrombopoietin mimetic plus immunosuppressive therapy<br>The intervention group will be given cyclosporin A plus thrombopoietin (TPO) mimetic starting with 50 mg orally daily that would be increased or decreased according to response, for 3-months. Patients will be kept on weekly follow up visits and assessed by peripheral hemogram . | Drug: Combination of thrombopoietin mimetic and cyclosporin A<br>* This is a controlled interventional study that will be carried out in the Clinical Hematology Unit, at the Department of Internal Medicine , Assiut University Hospital. Patients will be recruited among those who attending the outpatient clinic or admitted in the unit.<br>* Other names: Combination of Eltrombopag plus cyclosporin A;|
| No Intervention: Immunosuppressive therapy<br>A comparative group will be collected retrospectively and treated with cyclosporin A alone as standard. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with hematologjc response | Platelet number ( time frame(2-3 months) : Increase plt count 20, 000 or more from baseline or independence of platelet transfusion for 2 months Hemoglobin percent (time frame (2-3 months): increase Hb by 1.5 g/dl from baseline or reduction 4 units of packed red blood cell transfusions for 2- months C) Absolute neutrophilic count response (time frame (2-3 months): increase absolute neutrophil count by 500 per microliter from baseline. d) Bone marrow cellularity (time frame (2-3 months): increase bone marrow cellularity from baseline | 2-3months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with one of the following | Toxicity: development of toxicity leading to cessation of treatment Evolution: evolution to paroxysmal nocturnal hemoglobinuria , myelodysplastic syndrome or acute leukemia Bleeding and cytopenias that met the criteria for severe aplastic anemia and require transfusions | 2-3months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
thrombopoietin mimetic, Egyptian, Aplastic