Overview

Eltrombopag for Moderate Aplastic Anemia

Status:
Active, not recruiting
Trial end date:
2025-03-30
Target enrollment:
0
Participant gender:
All
Summary
Background: - Moderate aplastic anemia is a blood disease which may require frequent blood and platelet transfusions. Sometimes patients with this disease can be treated with immunosuppressive drugs. Not all patients respond and not all patients are suitable for this treatment. - Thrombopoietin (TPO) is a protein made by the body. The bone marrow needs TPO to produce platelets. TPO may also be able to stimulate bone marrow stem cells to produce red cells and white cells. However, TPO cannot be given by mouth. This has led researchers to develop the drug eltrombopag, which acts in the same way and can be given by mouth. Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and in patients with other chronic blood diseases, including severe aplastic anemia. Researchers are interested in looking at whether eltrombopag can be given to people with moderate aplastic anemia and significantly low blood cell counts. Objectives: - To evaluate the safety and effectiveness of eltrombopag in people with moderate aplastic anemia or patients with bone marrow failure and unilineage cytopenia who need treatment for significantly low blood cell counts. Eligibility: - People at least 2 years of age who have moderate aplastic anemia or bone marrow failure and unilineage cytopenia,and significantly low blood cell counts. Design: - Patients will be screened with a physical examination, medical history, blood tests, a bone marrow biopsy, and an eye exam. - Patients will receive eltrombopag by mouth once a day. - Patients will have weekly blood tests to monitor the effectiveness of the treatment and adjust the dose in response to possible side effects. - Patients may continue to take eltrombopag if their platelet count or hemoglobin increases, their requirement for platelet or blood transfusion decreases after 16 to 20 weeks of treatment, and there have been no serious side effects. Access to the drug will continue until the study is closed. Patients will be asked to return for a follow-up visit 6 months after the last dose of medication.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Criteria
- INCLUSION CRITERIA:

Current diagnosis of moderate aplastic anemia or unilineage bone marrow failure disorders.

- Moderate aplastic anemia is defined as aplastic anemia (hypocellular bone marrow for
age) with no evidence for other disease processes causing marrow failure, and
depression of at least two out of three blood counts below the normal values:

- ANC less than or equal to 1200/mm(3)

- platelet count less than or equal to 70,000/mm(3)

- anemia with hemoglobin less than or equal to 8.5 g/dL and absolute reticulocyte
count less than or equal to 60,000/mm(3) in transfusion-dependent patients but
not fulfilling the criteria for severe disease defined by depression of two of
the three peripheral counts:

- ANC less than or equal to 500/mm(3)

- platelet count less than or equal to 20,000/mm(3)

- reticulocyte count less than or equal to 60,000/mm(3)

- Unilineage bone marrow failure disorders are defined:

- Hemoglobin less than 8.5 g/dL and reticulocyte count less than 60,000 or red cell
transfusion dependent and hypocellular to normocellular bone marrow for age with
significantly reduced erythroid precursors.

- OR thrombocytopenia less than or equal to 30,000/uL or platelet transfusion
dependent and hypocellular to normocellular bone marrow for age with reduced
megakaryocytes.

- No evidence of viral or drug suppression of the marrow, dysplasia, or underproduction
anemias secondary to B12, folate, iron or other reversible causes.

Platelet transfusion dependent is defined as the need for platelet transfusion due to
platelet counts of < 10,000/microL with no bleeding (prophylactic transfusion) or <
20,000/microL with bleeding (therapeutic transfusion). Red cell transfusion dependent is
defined as transfusion of greater than 4 units of blood in the 8 weeks prior to study
entry.

Age greater than or equal to 2 years old

Weight greater than 12 kg

EXCLUSION CRITERIA:

Known diagnosis of Fanconi anemia

Counts that meet criteria for severe aplastic anemia

Infection not adequately responding to appropriate therapy

HIV positivity

Creatinine > 2.5 mg/dL

Bilirubin > 2.0 mg/dL, including congenital abnormalities in the bilirubin count

SGOT or SGPT >5 times the upper limit of normal

Hypersensitivity to eltrombopag or its components

Female subjects who are nursing or pregnant or are unwilling to take oral contraceptives or
refrain from pregnancy if of childbearing potential

Evidence of an active malignant hematological or clonal disorder, or abnormal cytogenetic
studies of the bone marrow performed within 12 weeks of study entry.

Unable to understand the investigational nature of the study or give informed consent or
does not have a legally authorized representative or surrogate that can provide informed
consent

Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious,
or metabolic disease of such severity that it would preclude the patient's ability to
tolerate protocol therapy, or that death within 7-10 days is likely.

Treatment with horse or rabbit ATG or Campath within 6 months of study entry.

Treatment with cytokines such as G-CSF or Erythropoietin.

Subjects with known cirrhosis in severity that would preclude tolerability of eltrombopag
as evidenced by albumin less than 35g/L.

Life expectancy of less than 3 months

Patients with an active diagnosis of cancer who have received chemotherapeutic treatment or
other specific antineoplastic drugs or radiation therapy within 6 months of study entry.

Unable to take investigational drug