A Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With International Prognostic Scoring System (IPSS) Intermediate-1, Intermediate-2 or High-risk Myelodysplastic Syndromes (MDS)

Status:	Terminated
Conditions:	Blood Cancer, Blood Cancer, Hematology
Therapuetic Areas:	Hematology, Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	12/14/2017
Start Date:	June 10, 2014
End Date:	April 30, 2016

A Randomized, Double-blind, Placebo-controlled, Phase III, Multi-centre Study of Eltrombopag or Placebo in Combination With Azacitidine in Subjects With IPSS Intermediate-1, Intermediate 2 and High-risk Myelodysplastic Syndromes (MDS) SUPPORT: A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine

Eltrombopag olamine (SB-497115-GR) is an orally bioavailable, small molecule thrombopoietin
receptor agonist that may be beneficial in medical disorders associated with
thrombocytopenia. Eltrombopag has been shown to increase platelet counts in patients with
thrombocytopenia from various etiologies (Idiopathic thrombocytopenic purpura [ITP], liver
disease, aplastic anemia and chemotherapy induced thrombocytopenia). Approximately 350
subjects will be randomized in a 1:1 ratio (175 into the eltrombopag arm and 175 into the
placebo arm). Approximately 55 subjects will be enrolled into the azacitidine. Subjects with
intermediate-1, intermediate-2 or high risk MDS by IPSS, and baseline platelet count of <75
Giga (10^9) per liter (Gi/L) will only be enrolled. This is a randomized, double-blind,
parallel group, placebo-controlled study designed to explore the platelet supportive care
effects of eltrombopag versus placebo in combination with the standard of care
hypomethylating agent, azacitidine. 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. Key secondary endpoints
include overall survival, disease response, and disease progression.

Inclusion Criteria:

- Age >=18 years (For subjects in Taiwan, Age >= 20 years)

- MDS by World Health Organization (WHO) or French-American-British (FAB) classification

- Intermediate 1, intermediate 2 or high risk MDS by IPSS

- At least one platelet count < 75 Gi/L

- Eastern Cooperative Oncology Group (ECOG) Status 0-2

- Adequate baseline organ function defined by the criteria below: total bilirubin =<
1.5x the upper limit of normal (ULN) except for Gilbert's syndrome or cases clearly
not indicative of inadequate liver function (i.e. elevation of indirect [haemolytic]
bilirubin in the absence of alanine aminotransferase [ALT] abnormality); ALT =<
2.5xULN; creatinine =< 2.5xULN

- Subjects with a corrected QT interval (QTc) <450 milliseconds (msec) or <480msec for
subjects with bundle branch block. The QTc is the QT interval corrected for heart rate
according to Fridericia's formula (QTcF), machine or manual overread. For subject
eligibility and withdrawal, QTcF will be used. For purposes of data analysis, QTcF
will be used. The QTc should be based on single or averaged QTc values of triplicate
electrocardiograms (ECGs) obtained over a brief recording period

- Subject is able to understand and comply with protocol requirements and instructions

- Subject has signed and dated informed consent

- Women must be either of non-child bearing potential, or women with child-bearing
potential and men with reproductive potential must be willing to practice acceptable
methods of birth control during the study

- Women of childbearing potential must have a negative serum or urine pregnancy test
within 7 days of first dose of study treatment and agree to use effective
contraception during the study and for 3 months following the last dose of study
treatment

- Men with a female partner of childbearing potential must have either had a prior
vasectomy or agree to use effective contraception from time of randomization until 16
weeks after the last dose of study treatment

- French subjects: 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:

- Previous treatment with hypomethylating agent or induction chemotherapy for MDS

- Proliferative type chronic myelomonocytic leukemia with white blood cell count >12
Gi/L at any time during the 28 days before Day 1

- History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor
(TPO-R) agonists

- Previous allogeneic stem-cell transplantation

- 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

- Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of investigational product (eltrombopag/placebo)

- Active and uncontrolled infections, including hepatitis B or C

- Human Immunodeficiency Virus (HIV) infection

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to eltrombopag or its excipient, or azacitidine, that
contraindicates the subjects' participation

- Pregnant or lactating female

- Any serious and/or unstable pre-existing medical condition (including any advanced
malignancy other than the disease under study), psychiatric disorder, or other
conditions that could interfere with subject's safety, obtaining informed consent or
compliance with the study procedures

- French subjects: the French subject has participated in any study using an
investigational drug during the previous 30 days

We found this trial at

sites

Novartis Investigative Site

Anderson, Indiana 46016

from

Anderson, IN