Eltrombopag for Moderate Aplastic Anemia
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|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
|First Submitted Date ICMJE||April 1, 2011|
|First Posted Date ICMJE||April 4, 2011|
|Results First Submitted Date ICMJE||March 29, 2019|
|Results First Posted Date ICMJE||April 23, 2019|
|Last Update Posted Date||October 20, 2020|
|Study Start Date ICMJE||April 1, 2011|
|Actual Primary Completion Date||March 30, 2018 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||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
|Original Primary Outcome Measures ICMJE
||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. [ Time Frame: 16 weeks ]|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE
||Incidence of bleeding, changes in serum thrombopoietin level, and health related quality of life (as measured by the Medical Outcomes Study 36-Item Short Form General Health Survey, version 2 [SF36v2] Quality-Metric) measured at 16 weeks. [ Time Frame: 16 weeks ]|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Eltrombopag for Moderate Aplastic Anemia|
|Official Title ICMJE||A Pilot Study of a Thrombopoietin-Receptor Agonist (TPO-R Agonist), Eltrombopag, in Moderate Aplastic Anemia Patients|
- 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.
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 ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Eltrombopag
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.
|Study Arms ICMJE||Experimental: Eltrombopag
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.
Intervention: Drug: Eltrombopag
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Active, not recruiting|
|Actual Enrollment ICMJE
|Original Estimated Enrollment ICMJE
|Estimated Study Completion Date ICMJE||March 30, 2025|
|Actual Primary Completion Date||March 30, 2018 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
Current diagnosis of moderate aplastic anemia or unilineage bone marrow failure disorders.
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
Known diagnosis of Fanconi anemia
Counts that meet criteria for severe aplastic anemia
Infection not adequately responding to appropriate therapy
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
|Ages ICMJE||2 Years to 100 Years (Child, Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT01328587|
|Other Study ID Numbers ICMJE||110134
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )|
|Study Sponsor ICMJE||National Heart, Lung, and Blood Institute (NHLBI)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||September 2020|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP