Eltrombopag for Moderate Aplastic Anemia
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01328587|
Recruitment Status : Active, not recruiting
First Posted : April 4, 2011
Results First Posted : April 23, 2019
Last Update Posted : October 20, 2020
- 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.
- 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.
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Moderate Aplastic Anemia Unilineage Bone Marrow Failure Disorders||Drug: Eltrombopag||Phase 2|
Moderate aplastic anemia (MAA) is a blood disease which can be effectively treated with immunosuppressive drug regimens. However, a significant number of patients have persistent cytopenias. Currently, the treatment of these patients is regular transfusion, which are expensive, inconvenient, and associated with serious side effects related to iron overload, or cytokines such as erythropoietin or G-CSF, which are expensive, and not effective in many patients.
Thrombopoietin (TPO) is a protein made by the body that is important for normal production of platelets by the bone marrow. TPO may also be able to stimulate bone marrow stem cells to produce red cells and white cells. TPO cannot be given by mouth, and as an alternative, a drug, eltrombopag, has been designed that acts in the same way as TPO but is stable and active when given by mouth. Eltrombopag has been shown to safely increase platelet numbers in healthy volunteers and in patients with chronic immune thrombocytopenic purpura (ITP). It has been recently granted accelerated approval by FDA on November 20, 2008 for the treatment of patients with chronic immune thrombocytopenic purpura (ITP) who have had an insufficient response to standard therapies.
We have previously shown encouraging results when eltrombopag is used to treat patients with severe aplastic anemia, with some patients responding with increases in platelets, red cells and white cells. Given these encouraging early preliminary results in our clinical trial using eltrombopag in Severe Aplastic Anemia (SAA), and low toxicity and ease of administration of this drug, we now propose a non-randomized pilot phase II study of eltrombopag in moderate aplastic anemia patients with clinically significant thrombocytopenia or anemia. Patients with MAA may not reach criteria for SAA, but none the less may be transfusion-dependent or have significant symptoms from cytopenias. We hypothesize that patients with MAA as compared to SAA may have a better chance of response, due to better residual marrow function in MAA patients compared to SAA.
Eligible patients can have treated or untreated MAA, as well as counts meeting criteria for MAA following a partial response to treatment with immunosuppression for SAA. We will also include patients with bone marrow failure and unilineage cytopenia. Treatment response for the platelet lineage is defined as platelet count increases to 20,000/microL above baseline at 16 to 20 weeks, or freedom from platelet transfusions for greater than or equal to 8 weeks in transfusion-dependent patients. For patients with anemia (untransfused hemoglobin less than or equal to 8.5 g/dL), a treatment response will be an increase in Hb by greater than or equal to 1.5g/dl at four months, measured on at least 2 serial measurements and sustained for 1 month or more without transfusion support OR for transfusion dependent patients, reduction of units of RCC transfused by 50 percent/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks or transfusion independence (no transfusions for greater than or equal to 8 weeks). Subjects with evidence for a clinical response in any lineage at 16 weeks but not yet meeting full primary endpoint response criteria, and who are tolerating investigational treatment, may receive an additional 4 weeks of eltrombopag and be reassessed after 20 weeks. At that time, if they meet primary endpoint response criteria, they will be eligible to enter the extended access part of the study. If they do not meet primary endpoint response criteria, eltrombopag will be discontinued.
The primary objective is to assess the safety and efficacy of the oral thrombopoietin receptor agonist (TPO-R agonist) eltrombopag in moderate aplastic anemia patients or patients with bone marrow failure and unilineage cytopenia. Secondary objectives include the analysis of the incidence and severity of bleeding, clonal evolution to PNH, clonal chromosomal population in bone marrow, myelodysplasia by morphology, or acute leukemia and the impact on quality of life.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Moderate Aplastic Anemia Patients|
|Study Start Date :||April 1, 2011|
|Actual Primary Completion Date :||March 30, 2018|
|Estimated Study Completion Date :||March 30, 2025|
Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 50mg/day (East Asian ancestry 25mg/day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.
Eltrombopag will be administered for 16 to 20 weeks at a starting dose of 150mg/day (East Asian ancestry 75mg /day). The dose will decreased and increased (maximum dose 300mg/day) based on safety and response.
- Proportion of Drug Responders [ Time Frame: 16-20 weeks from start of drug ]The portion of drug responders as defined by changes in the platelet count and/or platelet transfusion requirements or hemoglobin and/or PRBC transfusion requirements and the toxicity profile as measured using the CTCAE criteria. Treatment response for the platelet lineage is defined as an absolute increase of ≥20x10^9/L above baseline at 16 or 20 weeks, measured on at least two serial measurements performed one week apart and sustained for 1 month or more without support of platelet transfusions, or for transfusion dependent patients stable platelet counts with transfusion independence for ≥ 8 weeks. For patients with anemia (untransfused hemoglobin ≤ 8.5 g/dL), a treatment response will be an increase in Hb by ≥1.5g/dL at four months, measured on at least 2 serial measurements and sustained for 1 month or more without transfusion support OR for transfusion dependent patients, reduction of units of RCC transfused by 50%/8 weeks compared with the pretreatment transfusion number in th
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01328587
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Cynthia E Dunbar, M.D.||National Heart, Lung, and Blood Institute (NHLBI)|