Clinical trial NCT03896971: Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia
Official title: Treatment With Thrombopoietin Mimetic Plus Immunosuppressive Therapy in Egyptian Patients With Aplastic Anaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Aplastic Anemia
Keywords: thrombopoietin mimetic
Egyptian
Aplastic
Lead sponsor: Assiut University
Sponsor class: OTHER
Collaborators: name: Assiut University
First posted: 2019-04-01
Enrollment: 66
Sex: ALL
Minimum age (years): 16
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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 :

1. To evaluate the efficacy, tolerability and toxicity of the combination of thrombopoietin mimetic and immunosuppressive therapy in Egyptian patients with AA.
2. To study the influence of this combination on patients' quality of life.
3. 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.

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

Primary outcomes:
measure: Number of patients with hematologjc response
timeFrame: 2-3months
Secondary outcomes:
measure: Number of patients with one of the following
timeFrame: 2-3months
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut university hospital Internal Medicine Department Hematology and BMT Unit
Study officials:
affiliation: Assiut University
name: Safinaz Hussien, MD
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Sawsan A Abdelaal, M.B.B.Ch
role: PRINCIPAL_INVESTIGATOR
References:
citation: Scheinberg P, Cooper JN, Sloand EM, Wu CO, Calado RT, Young NS. Association of telomere length of peripheral blood leukocytes with hematopoietic relapse, malignant transformation, and survival in severe aplastic anemia. JAMA. 2010 Sep 22;304(12):1358-64. doi: 10.1001/jama.2010.1376.
citation: Frickhofen N, Kaltwasser JP, Schrezenmeier H, Raghavachar A, Vogt HG, Herrmann F, Freund M, Meusers P, Salama A, Heimpel H. Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group. N Engl J Med. 1991 May 9;324(19):1297-304. doi: 10.1056/NEJM199105093241901.
citation: Frickhofen N, Heimpel H, Kaltwasser JP, Schrezenmeier H; German Aplastic Anemia Study Group. Antithymocyte globulin with or without cyclosporin A: 11-year follow-up of a randomized trial comparing treatments of aplastic anemia. Blood. 2003 Feb 15;101(4):1236-42. doi: 10.1182/blood-2002-04-1134. Epub 2002 Oct 10.
citation: Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.
citation: Kuter DJ. Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med. 2009;60:193-206. doi: 10.1146/annurev.med.60.042307.181154.
citation: Desmond 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.