Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia

Aplastic Anemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03896971
• Other study ID #: SKhaled19
• Status: Completed
• Phase: Phase 4
• Start date: November 15, 2019
• Est. completion date: June 1, 2021

Study information

• Verified date: September 2021
• Source: Assiut University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: June 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Anemia
• Anemia, Aplastic
• Aplastic Anemia

Intervention

Drug:
• Combination of thrombopoietin mimetic and cyclosporin A
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.

Locations

Country	Name	City	State
Egypt	Assiut university hospital Internal Medicine Department Hematology and BMT Unit	Assiut

Sponsors (2)

Lead Sponsor	Collaborator
Safaa AA Khaled	Assiut University

Country where clinical trial is conducted

Egypt, 

References & Publications (6)

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. — View 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. Epub 2002 Oct 10. — View 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. — View Citation

Kuter DJ. Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. Annu Rev Med. 2009;60:193-206. Review. — View 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. — View 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. Erratum in: JAMA. 2010 Nov 3;304(17):1901. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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