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Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia

Primary Purpose

Aplastic Anemia

Status
Completed
Phase
Phase 4
Locations
Egypt
Study Type
Interventional
Intervention
Combination of thrombopoietin mimetic and cyclosporin A
Sponsored by
Safaa AA Khaled
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Aplastic Anemia focused on measuring thrombopoietin mimetic, Egyptian, Aplastic

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Assiut university hospital Internal Medicine Department Hematology and BMT Unit

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Thrombopoietin mimetic plus immunosuppressive therapy

Immunosuppressive therapy

Arm Description

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 .

A comparative group will be collected retrospectively and treated with cyclosporin A alone as standard.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
March 21, 2019
Last Updated
September 28, 2021
Sponsor
Safaa AA Khaled
Collaborators
Assiut University
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1. Study Identification

Unique Protocol Identification Number
NCT03896971
Brief Title
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

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
November 15, 2019 (Actual)
Primary Completion Date
December 1, 2020 (Actual)
Study Completion Date
June 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Safaa AA Khaled
Collaborators
Assiut University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia
Keywords
thrombopoietin mimetic, Egyptian, Aplastic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thrombopoietin mimetic plus immunosuppressive therapy
Arm Type
Experimental
Arm Description
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 .
Arm Title
Immunosuppressive therapy
Arm Type
No Intervention
Arm Description
A comparative group will be collected retrospectively and treated with cyclosporin A alone as standard.
Intervention Type
Drug
Intervention Name(s)
Combination of thrombopoietin mimetic and cyclosporin A
Other Intervention Name(s)
Combination of Eltrombopag plus cyclosporin A
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of patients with hematologjc response
Description
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
Time Frame
2-3months
Secondary Outcome Measure Information:
Title
Number of patients with one of the following
Description
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
Time Frame
2-3months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Safinaz Hussien, MD
Organizational Affiliation
Assiut University
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Sawsan A Abdelaal, M.B.B.Ch
Organizational Affiliation
Assiut University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Assiut university hospital Internal Medicine Department Hematology and BMT Unit
City
Assiut
ZIP/Postal Code
71515
Country
Egypt

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
20858879
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.
Results Reference
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PubMed Identifier
2017225
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.
Results Reference
background
PubMed Identifier
12393680
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.
Results Reference
background
PubMed Identifier
12622583
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.
Results Reference
background
PubMed Identifier
19642221
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.
Results Reference
background
PubMed Identifier
24345753
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.
Results Reference
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Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia

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