Advanced Myelodysplastic Syndrome (MDS) or secondary Acute Myeloid Leukemia after MDS MedDRA version: 14.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GlaxoSmithKline
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult subjects (18 years of age or older) with advanced MDS, sAML/MDS, or de novo AML with >=10% and 7 days during screening. 7. During the 4 weeks prior to randomization, subjects must have a baseline bone marrow examination including the following: a. cytomorphology to confirm bone marrow blasts between 10-50%, b. cytogenetics (provide only most prevalent abnormal clone), The results of the above tests are required prior to subject randomization 8. Supportive/palliative therapies such as cytokines (except for IL-11; oprelvekin), valproic acid, all-trans retinoic acid or mild chemotherapy are allowed if part of the local SOC, provided those therapies have been at a stable dose for 4 weeks. If the subject chooses to discontinue these therapies prior to study entry, they must be completed 4 weeks prior to enrollment into this study, unless the therapy is discontinued due to lack of efficacy. Erythropoiesis-timulatingagents (ESAs) in anemic subjects or granulocyte colony-stimulating factor (G-CSF) in subjects with severe neutropenia and recurrent infections are allowed during the study as per accepted standards. Subjects who enter the study on ESAs or G-CSF should continue at the same dose schedule until the optimal dose of study medication has been established. 9. ECOG Status 0-3. 10. Subject is able to understand and comply with protocol requirements and instructions. 11. Subject has signed and dated informed consent. 12. Prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) must be within 80 to 120% of the normal range at baseline. 13. Adequate baseline organ function defined by the criteria below: • total bilirubin (except for Gilbert’s Syndrome) <=1.5xULN • ALT and AST <=3xULN • creatinine
Exclusion criteria
Exclusion criteria: 1. Subjects with a diagnosis of acute promyelocytic leukemia. 2. History of treatment for cancer (other than MDS, sAML/MDS or or de novo AML) with systemic chemotherapy and/or radiotherapy within the last 2 years. 3. History of treatment with romiplostim or other TPO-R agonists. 4. Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block). 5. Bone marrow fibrosis that leads to an inability to aspirate marrow for assessment. 6. Spleen size >14 cm (length as per ultrasound examination). 7. Leukocytosis =25,000/uL prior to Day 1 of study medication. 8. Female subjects who are nursing or pregnant (positive serum or urine ß-human chorionic gonadotropin [ß-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. 12. Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV). 13. Subjects with liver cirrhosis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of eltrombopag when administered to subjects with advanced MDS, sAML/MDS or de novo AML with 10-50% bone marrow blasts.;Secondary Objective: To evaluate the effect of eltrombopag on platelet counts. To evaluate the effect of eltrombopag on the need for platelet transfusions. To evaluate the effect of eltrombopag on the duration of platelet transfusion independence. To evaluate the effect of eltrombopag on bleeding events. To evaluate the effect of eltrombopag on overall survival (OS). To evaluate eltrombopag population pharmacokinetics. ;Primary end point(s): Safety and tolerability parameters including non-hematological laboratory Grade 3/Grade 4 toxicities, change in bone marrow blast counts from baseline and adverse events reporting. | — |
Countries
Denmark, France, Germany, United Kingdom
Outcome results
None listed