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A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia (ASPIRE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01440374
First received: September 15, 2011
Last updated: November 13, 2014
Last verified: November 2014

September 15, 2011
November 13, 2014
September 2011
December 2014   (final data collection date for primary outcome measure)
Reduction in clinically relevant thrombocytopenic events [ Time Frame: weeks 5-12 ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01440374 on ClinicalTrials.gov Archive Site
  • Hematologic improvement (change in platelets, neutrophils and hemoglobin) [ Time Frame: baseline and weekly for 3 months ] [ Designated as safety issue: No ]
  • Assessment of platelet counts [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Need for platlet transfusions [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Duration of platelet transfusion-independence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • The occurrence and severity of bleeding, measured using the WHO Bleeding Scale [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Disease response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Safety as measured by number of adverse events. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • FACT-TH-18 and the EQ-5D Questionnaires [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Disease progression [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Evaluate MDS and AML disease response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Evaluate MDS and AML disease progression [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Evaluate overall survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Hematologic improvement (change in platelets, neutrophils and hemoglobin) [ Time Frame: baseline and weekly for 3 months ] [ Designated as safety issue: No ]
  • Assessment of platelet counts [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Number of platelet transfusions [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Duration of platelet transfusion-independence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • The occurrence and severity of bleeding, measured using the WHO Bleeding Scale [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Disease response [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Safety as measured by number of adverse events. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • FACT-TH-18 and the EQ-5D Questionnaires [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Disease progression [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia
A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia (Part 1: Open-label, Part 2: Randomized, Double-blind, Part 3: Extension)

This is a worldwide, three-part (Part 1: open-label, Part 2: randomized, double-blind, Part 3: extension), multi-center study to evaluate the effect of eltrombopag in subjects with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who have thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy. This objective will be assessed by a composite primary endpoint that consists of the following: the proportion of ≥Grade 3 hemorrhagic adverse events, or platelet counts <10 Gi/L, or platelet transfusions. Patients with MDS or AML and Grade 4 thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy will be enrolled in the study. No low or intermediate-1 risk MDS subjects will be enrolled in the study.

Subjects must have had at least one of the following during the 4 weeks prior to enrolment: platelet count <10 Gi/L, platelet transfusion, or symptomatic hemorrhagic event. Supportive standard of care (SOC), including hydroxyurea, will be allowed as indicated by local practice throughout the study. The study will have 3 sequential parts. Subjects who are enrolled in Part 1 (open-label) cannot be enrolled in Part 2 of the study (randomized, double-blind); however, subjects who complete the treatment period for Part 1 or Part 2 (8 and 12 weeks, respectively) will continue in Part 3 (extension) if the investigator determines that the subject is receiving clinical benefit on treatment.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Thrombocytopaenia
  • Drug: eltrombopag
    100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
    Other Name: Promacta
  • Drug: placebo
    100 mg matching placebo daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg matching placebo (150 mg for subjects of East Asian heritage)
  • Experimental: Part 1, Open Label
    100 mg daily (50 mg for subjects of East Asian heritage), intrasubject dose escalations to a maximum dose 300 mg (150 mg for subjects of East Asian heritage) are allowed.
    Intervention: Drug: eltrombopag
  • Experimental: Part 2, eltrombopag arm
    100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
    Intervention: Drug: eltrombopag
  • Experimental: Part 2, placebo arm
    100 mg matching placebo daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg matching placebo (150 mg for subjects of East Asian heritage)
    Intervention: Drug: placebo
  • Experimental: part 3 extension
    100 mg daily (50 mg for subjects of East Asian heritage), intra-subject dose escalations to a maximum dose of 300 mg (150 mg for subjects of East Asian heritage)
    Intervention: Drug: eltrombopag
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
150
December 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%) with thrombocytopenia due to bone marrow insufficiency from the disease or prior treatment. Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded
  • Subjects must have Grade 4 thrombocytopenia (platelet counts <25 Gi/L) due to bone marrow insufficiency (or Grade 4 thrombocytopenia, but platelet count greater than or equal to 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 <10 Gi/L. Subjects whose thrombocytopenia below 10 Gi/L is due to causes other than bone marrow insufficiency (e.g., fever, infection, autoimmune disease) are not eligible.
  • Subjects must have platelet count, bleeding and platelet transfusion data available over a period of at least 4 weeks prior to randomization.
  • Prior systemic treatment for malignancy, with the exception of hydroxyurea, 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.
  • Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
  • Subjects must be stable and, in the opinion of the investigator, be expected to complete a 12 week treatment period.
  • ECOG Status 0-2.
  • Subject must be able to understand and comply with protocol requirements and instructions.
  • Subject has signed and dated an informed consent form.
  • Adequate baseline organ function defined by the criteria below: total bilirubin ≤ 1.5xULN except for Gilbert's syndrome or cases clearly not indicative of inadequate liver function (i.e. elevation of indirect (hemolytic) bilirubin in the absence of ALT abnormality), ALT ≤ 3xULN, creatinine ≤ 2.5xULN
  • 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 prior to the first dose of study treatment.
  • 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:

  • Subjects with MDS and an IPSS of low or intermediate-1 risk at screening.
  • Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm.
  • History of treatment with romiplostim or other TPO-R agonists.
  • Subjects with a QTc >480 msec (QTc >510 msec for subjects with Bundle Branch Block).
  • Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication.
  • 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.
  • 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.
  • Current alcohol or drug abuse.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
  • Subjects infected with Human Immunodeficiency Virus (HIV).
  • Subjects with liver cirrhosis (as determined by the investigator).
  • Subjects receiving or planned to receive any prohibited medication.
  • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidone, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects' participation.
  • In France, subjects who have participated in any study using an investigational drug during the previous 30 days.
Both
18 Years and older
No
Contact: US GSK Clinical Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
United States,   Argentina,   Belgium,   Brazil,   Canada,   Czech Republic,   Germany,   Greece,   Hong Kong,   Hungary,   Ireland,   Israel,   Italy,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Puerto Rico,   Russian Federation,   Spain,   Taiwan,   Thailand
 
NCT01440374
114968
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP