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 August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01440374
First received: September 15, 2011
Last updated: August 21, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Thrombocytopaenia
Drug: eltrombopag
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Reduction in clinically relevant thrombocytopenic events [ Time Frame: weeks 5-12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 150
Study Start Date: September 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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)
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
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)
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 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)
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440374

Contacts
Contact: US GSK Clinical Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

  Show 108 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01440374     History of Changes
Other Study ID Numbers: 114968
Study First Received: September 15, 2011
Last Updated: August 21, 2014
Health Authority: Spain: Agencia Espanola de Medicamentos y Productos Sanitarios
Netherlands: Centrale Commissie Mensgesbonden Onderzoek (Central Committee on Research Involving Human Subjects) Den Haag (The Hague), The Netherlands
Korea: Food and Drug Administration
Belgium: FAGG
Mexico: Secretaría de Salud
Taiwan: Food and Drug Administration, Department of Health, Executive Yuan
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Thailand: Food and Drug Administration
United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Thailand: Ministry of Public Health
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Italy: Ministry of Health
Hong Kong: Department of Health
Israel: State of Israel Ministry of Health, Health Technology and Infrastructure Administration, Medical Devices Department
Brazil: ANVISA - Agência Nacional de Vigilância Sanitaria
Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Russian Federation: Ministry of Health and social development of Russian Federation, Federal
India: Drugs Controller General of India (DCGI)
Czech Republic: State Institute for Drug Control

Additional relevant MeSH terms:
Thrombocytopenia
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Blood Platelet Disorders

ClinicalTrials.gov processed this record on August 28, 2014