Health Condition 1: null- Acute Myeloid Leukemia
Conditions
Interventions
Intervention1: Eltrombopag: Eltrombopag 100 mg once daily has been selected as the starting dose for this study.
Subsequent dose adjustments will be dependent on each subjectâ??s platelet counts.
Inte
Sponsors
GlaxoSmithKline Pharmaceuticals Ltd
Eligibility
Inclusion criteria
Inclusion criteria: 1. Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts prior treatment. Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded. 2. Subjects must have Grade 4 thrombocytopenia (platelet counts bone marrow insufficiency (or platelet count >=25 Gi/L due to platelet transfusion). In addition, subjects must have had at least one of the following during the 4 week screening period: platelet transfusion, or symptomatic bleeding or platelet count than bone marrow insufficiency (e.g., fever, infection, autoimmune disease) are not eligible. 3. Subjects must have platelet count, bleeding and platelet transfusion data available over a period of at least 4 weeks prior to randomization. 4. Prior systemic treatment for malignancy, with the exception of hydroxyurea (see Section 6.1.2), must have been discontinued prior to entry into the study: • at least 4 weeks before Day 1 for the following: chemotherapy, demethylating agents (azacitidine or decitabine), lenalidomide, thalidomide, clofarabine and IL- 11(oprelvekin); • at least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin.5. Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT. 6. Subjects must have stable disease (as defined by treatment guidelines and investigator discretion) and, in the opinion of the investigator, must be expected to complete a 12 week treatment period. 7. ECOG Status 0-2. 8. Subject must be able to understand and comply with protocol requirements and instructions. 9. Subject has signed and dated an informed consent form. 10. Adequate baseline organ function defined by the criteria below: • total bilirubin indicative of inadequate liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of ALT abnormality) • ALT • creatinine definition) or women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study (See Section 7.3.12.2, for acceptable methods of birth control). Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment. 12. In France, a subject will be eligible for inclusion in this study only if either affiliated to, or a beneficiary of, a social security category.
Exclusion criteria
Exclusion criteria: 1. Subjects with MDS and an IPSS of low or intermediate-1 risk. 2. Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm. 3. History of treatment with romiplostim or other TPO-R agonists. 4. Subjects with a QTc 480 msec (QTc 510 msec for subjects with Bundle Branch Block) at baseline. 5. Subjects with a palpable spleen must have a splenic ultrasound to confirm spleen length is 6. Leukocytosis >=25,000/uL on Day 1 of treatment with study medication. 7. Subjects with known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator. 8. Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1. 9. Current alcohol or drug abuse. 10. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. 11. Active and uncontrolled infections (e.g. sepsis). 12. Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV). 13. Subjects with liver cirrhosis (as determined by the investigator). 14. Subjects receiving or planned to receive any prohibited medication (see Section 6.2).15. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidine, sodium starch glycolate, magnesium stearate,hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjectsâ?? participation. 16. In France, subjects who have participated in any study using an investigational drug during the previous 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective of this study is to determine the reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia and are treated with eltrombopag compared to those treated with placebo.Timepoint: The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate overall survival To evaluate the safety and tolerability of eltrombopag. To evaluate the effect of eltrombopag on medical resource utilization. To evaluate the effect of eltrombopag on health related quality of life. Timepoint: Overall survival Physical exam findings, clinical monitoring, vital signs, clinical laboratory tests, and adverse event reporting (including hemorrhagic and transfusion-related adverse events). Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage. FACT-TH-18 and the EQ-5D ;Secondary objectives compare the following in subjects treated with eltrombopag and placebo:Timepoint: Secondary endpoints compare the following in subjects treated with eltrombopag and placebo:;To evaluate the effect of eltrombopag on the duration of platelet transfusion independence. To evaluate the effect of eltrombopag on bleeding symptoms. To evaluate MDS and AML disease response To evaluate MDS and AML disease progression Timepoint: Duration of platelet transfusion-independence. The occurrence and severity of bleeding, measured using the WHO Bleeding Scale. Disease response Disease progression ;To evaluate the effect of eltrombopag on the need for platelet transfusions. To evaluate hematologic improvement To evaluate the effect of eltrombopag on platelet counts Timepoint: Number of platelet transfusions Hematologic improvement (platelets, neutrophils and hemoglobin) Assessment of platelet counts throughout the study | — |
Countries
Argentina, Belgium, Brazil, Canada, Czech Republic, Democratic People's Republic of Korea, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, Peru, Poland, Russian Federation, Spain, Taiwan, Thailand, United Kingdom, United States of America
Contacts
Public ContactKedar Nayak
GlaxoSmithKline Pharmaceuticals Limited
Outcome results
None listed