Combination of Thrombopoietin Mimetic and Immunosuppressive Therapy in Aplastic Anaemia

Safaa AA Khaled

Status and phase: Completed; Phase 4

Conditions: Aplastic Anemia

Treatments: Drug: Combination of thrombopoietin mimetic and cyclosporin A

Study type: Interventional

Funder types: Other

Identifiers

NCT03896971

SKhaled19

Details and patient eligibility

About

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

Full 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.

Enrollment: 66 patients

Sex: All

Ages: 16 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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66 participants in 2 patient groups

Thrombopoietin mimetic plus immunosuppressive therapy

Experimental group

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 .

Treatment:

Drug: Combination of thrombopoietin mimetic and cyclosporin A

Immunosuppressive therapy

No Intervention group

Description:

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