Thrombocytopenic patients with myelodysplastic syndromes MedDRA version: 16.1 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 16.1 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Revolade
Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ELTROMBOPAG
CAS Number: 496775-61-2
Current Sponsor code: SB-497115
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria. The eligibility criteria are to be met during the screening period, defined as the period up to 28 days prior to randomization on Day 1. 1. Age = 18 years. 2. Intermediate 1, intermediate 2 or high risk MDS by IPSS. 3. At least one platelet count =65 years) yes F.1.3.1 Number of subjects for this age range 192
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria at the time of randomization must not be enrolled in the study: 1. Previous treatment with hypomethylating agent or induction chemotherapy for MDS. 2. History of treatment with eltrombopag, romiplostim or other TPO-R agonists. 3. Previous allogeneic stem-cell transplantation. 4. 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. 5. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of investigational product (eltrombopag/placebo). 6. Active and uncontrolled infections, including hepatitis B or C. 7. Known Human Immunodeficiency Virus (HIV) infection. 8. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or its excipient, or azacitidine, that contraindicates the subjects’ participation. 9. Pregnant or lactating female. 10. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures. 11. French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the effect of eltrombopag versus placebo on the proportion of subjects who are platelet transfusion free during the first 4 cycles of azacitidine therapy.;Secondary Objective: Secondary objectives compare the following in subjects treated with eltrombopag/azacitidine versus placebo/azacitidine: Overall survival (OS) Disease Response Hematologic improvement (HI) Platelet and red blood cell (RBC) transfusions Bleeding adverse events (AEs) greater than Grade 3 Bleeding AEs Azacitidine treatment Safety and tolerability Health related quality of life (HRQoL) Medical resource utilization (MRU) Pharmacokinetic Characterize the pharmacokinetics of steady-state eltrombopag in subjects with MDS treated with azacitidine;Primary end point(s): Cycle 1-4 platelet transfusion independence (The proportion of subjects who are platelet transfusion free during Cycles 1-4 of azacitidine therapy) ;Timepoint(s) of evaluation of this end point: Primary endpoint to be evaluated once all subjects recruited into study have completed 6 cycles, withdrawn from the study or died. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints compare the following in subjects treated with eltrombopag/azacitidine versus placebo/azacitidine. OS Disease Response Disease response (per 2006 International Working Group (IWG) criteria) Duration of Disease Response Progression Free Survival Time to Progression Proportion of subjects that progress to AML Time to AML progression HI in platelets, neutrophils and haemoglobin (per 2006 IWG criteria) Duration of HI of platelets, neutrophils, and hemoglobin Number of platelet and RBC transfusions Duration of platelet and RBC transfusion independence Bleeding AEs greater than Grade 3 Azacitidine dose delays and dose reductions Evaluation of adverse event reporting (including bleeding and transfusion-related adverse events), and clinical laboratory tests EQ-5D-3L, EORTC-QLQ-C30, FACIT-Fatigue subscale, independent questions regarding the value of transfusion independence Event and use of site specific medical resources Pharmacokinetic Evaluation of covariates, and estimates of between and within subject variability;Timepoint(s) of evaluation of this end point: Once at least 140 subjects have completed 4 cycles, withdrawn or died: -Interim IDMC analysis for futility of the primary endpoint of Cycle 1-4 transfusion independence. The IDMC will also meet at predefined times to identify potential treatment harm Once all recruited 350 subjects have completed 6 cycles, withdrawn or died: -The primary endpoint of Cycle 1-4 transfusion independence will be tested. -Interim analysis for the key secondary endpoint of OS.* -Analysis of all other secondary endpoints Once 275 events (deaths) occur: -Final analysis for the key secondary endpoint of OS *The endpoint of OS will be tested only if the null hypothesis for the test of Cycle 1-4 transfusion independence is rejected. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Korea, Republic of, Mexico, Norway, Peru, Poland, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd.
Outcome results
None listed