Last updated: 11/03/2018 12:36:18
This product has been transferred to Novartis. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on clinicaltrials.gov.

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

GSK study ID
112121
Clinicaltrials.gov ID
NCT02158936
EudraCT ID
2013-000918-37
EU CT Number
Not applicable
Trial status
No longer a GSK study
No longer a GSK study
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Cycle 1-4 platelet transfusion independence (The proportion of subjects who are platelet transfusion free during Cycles 1-4 of azacitidine therapy)

Timeframe: 4 cycles (Cycle = 28 days)

Secondary outcomes:

Time to AML progression

Timeframe: Approximately 5.5 years

Duration of HI of platelets, neutrophils and hemoglobin

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Overall survival (OS)

Timeframe: Approximately 5.5 years

Proportion of subjects that progress to Acute Myeloid Leukemia (AML)

Timeframe: Approximately to 5.5 years

Disease Response categorized as CR, PR, or marrow CR, stable disease, disease progression, and as non-evaluable as per IWG criteria for MDS

Timeframe: Approximately 6 Cycles (Cycle = 28 days)

Bleeding adverse events (AEs) >= Grade 3

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Composite of PK parameters of Azacitidine (subset of 55 subjects) including Cmax, tmax, AUC(0-t), AUC(0-infinity), and t1/2

Timeframe: Samples will be collected on Cycle 2 Day 1 before the azacitidine dose and 15 min, 0.5, 1, 2, and 4 hours after the azacitidine dose

Medical resource utilization (MRU): Event and use of site specific medical resources

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Changes from baseline in all domains of European Organization for Research and Treatment of Cancer - Quality of Life questionnaire - 30 item (EORTC QLQ-C30)

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Duration of platelet and RBC transfusion independence

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Proportion of subjects with azacitidine dose delays and dose reductions

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Changes from baseline in all domains of Functional Assessment of Chronic Disease Therapy-fatigue subscale (FACIT-Fatigue)

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Number of platelet transfusion-free cycles

Timeframe: 6 cycles (Cycle = 28 days)

Hematologic improvement (HI) in platelets, neutrophils, and hemoglobin calculated based on the modified IWG criteria for MDS

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Changes from baseline in all domains of Euroquol-5 Dimensions of Health, 3 Response Levels (EQ-5D-3L™)

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Composite of pharmacokinetic (PK) parameters of Eltrombopag including evaluation of covariates, and estimates of between and within subject variability

Timeframe: Cycle 1, Week 2: Pre-dose, 1.5 and 3 hour post dose; Cycle 1, Week 3: 4, 5.5, and 7 hours post dose

Number of platelet and Red Blood Cells (RBC) transfusions

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Time to Progression

Timeframe: Approximately 5.5 years

Progression Free Survival

Timeframe: Approximately 5.5 years

Evaluation of Adverse event reporting (including bleeding and transfusion-related adverse events) and clinical laboratory tests

Timeframe: From Day 1 to 4-week follow-up (Approximate median 9 Cycles+4 weeks follow-up)

Duration of Disease Response

Timeframe: Approximately 5.5 years

Changes from baseline in all domains of independent questions regarding the value of transfusion independence

Timeframe: At 4 week follow-up

Interventions:
  • Drug: Eltrombopag
  • Drug: Placebo
  • Drug: Azacitidine
    • Enrollment:
    350
    Primary completion date:
    2016-08-12
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Thrombocytopaenia
    Product
    azacitidine, eltrombopag
    Collaborators
    Not applicable
    Study date(s)
    June 2014 to December 2017
    Type
    Interventional
    Phase
    2/3

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    none
    • Age >=18 years (For subjects in Taiwan, Age >= 20 years)
    • MDS by World Health Organization (WHO) or French-American-British (FAB)
    • 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
    Inclusion and exclusion criteria
    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

    Trial location(s)

    This study does not involve prospective enrollment of participants.

    Study documents

    No study documents available.

    Results overview

    Study Results yet to be posted

    Recruitment status
    No longer a GSK study
    Actual primary completion date
    Not applicable
    Actual study completion date
    Not applicable

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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