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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01440374
First received: September 15, 2011
Last updated: April 16, 2015
Last verified: April 2015
  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 ]

Enrollment: 163
Study Start Date: September 2011
Estimated Study Completion Date: January 2016
Primary Completion Date: March 2015 (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

  Hide Study Locations
Locations
United States, Arizona
GSK Investigational Site
Phoenix, Arizona, United States, 85016
United States, Arkansas
GSK Investigational Site
Hot Springs, Arkansas, United States, 71913
GSK Investigational Site
Jonesboro, Arkansas, United States, 72401
United States, California
GSK Investigational Site
Los Angeles, California, United States, 90095
GSK Investigational Site
Stanford, California, United States, 94305
United States, Florida
GSK Investigational Site
Jacksonville, Florida, United States, 32256
GSK Investigational Site
Orlando, Florida, United States, 32806
GSK Investigational Site
West Palm Beach, Florida, United States, 33401
United States, Georgia
GSK Investigational Site
Augusta, Georgia, United States, 30912
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
United States, Massachusetts
GSK Investigational Site
Boston, Massachusetts, United States, 02115
United States, Missouri
GSK Investigational Site
Kansas City, Missouri, United States, 64128
United States, New Jersey
GSK Investigational Site
Hackensack, New Jersey, United States, 07601
GSK Investigational Site
Voorhees, New Jersey, United States, 08043
United States, New York
GSK Investigational Site
Bornx, New York, United States, 10467
United States, Pennsylvania
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98108
United States, Wisconsin
GSK Investigational Site
Milwaukee, Wisconsin, United States, 53226
Argentina
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1431FWO
GSK Investigational Site
La Plata, Buenos Aires, Argentina, B1900AXI
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Argentina, C1025ABH
GSK Investigational Site
Ciudad Autónoma de Buenos Aires, Argentina, 1405
Belgium
GSK Investigational Site
Antwerpen, Belgium, 2060
GSK Investigational Site
Brasschaat, Belgium, 2930
GSK Investigational Site
Brugge, Belgium, 8000
GSK Investigational Site
Brussels, Belgium, 1000
GSK Investigational Site
Gent, Belgium, 9000
GSK Investigational Site
Leuven, Belgium, 3000
GSK Investigational Site
Yvoir, Belgium, 5530
Brazil
GSK Investigational Site
Goiânia - GO, Goiás, Brazil, 74605-050
GSK Investigational Site
Curitiba, Paraná, Brazil, 81520-060
GSK Investigational Site
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
GSK Investigational Site
Barretos, São Paulo, Brazil, 14784-400
GSK Investigational Site
Rio de Janeiro, Brazil, 20211-030
GSK Investigational Site
São Paulo, Brazil, 01236030
Canada, Nova Scotia
GSK Investigational Site
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
GSK Investigational Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
GSK Investigational Site
Montreal, Quebec, Canada, H3T 1E2
Czech Republic
GSK Investigational Site
Brno, Czech Republic, 625 00
GSK Investigational Site
Praha, Czech Republic, 128 20
GSK Investigational Site
Praha 10, Czech Republic, 100 34
GSK Investigational Site
Praha 2, Czech Republic, 128 08
Germany
GSK Investigational Site
Mannheim, Baden-Wuerttemberg, Germany, 68167
GSK Investigational Site
Stuttgart, Baden-Wuerttemberg, Germany, 70199
GSK Investigational Site
Goettingen, Niedersachsen, Germany, 37075
GSK Investigational Site
Duesseldorf, Nordrhein-Westfalen, Germany, 40225
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
GSK Investigational Site
Dresden, Sachsen, Germany, 01307
Greece
GSK Investigational Site
Athens, Greece, 11527
GSK Investigational Site
Heraklion, Crete, Greece, 71201
GSK Investigational Site
Ioannina, Greece, 45 500
GSK Investigational Site
Thessaloniki, Greece, 57010
Hong Kong
GSK Investigational Site
Chai Wan, Hong Kong
GSK Investigational Site
Shatin, New Territories, Hong Kong
Hungary
GSK Investigational Site
Budapest, Hungary, 1088
GSK Investigational Site
Debrecen, Hungary, 4012
GSK Investigational Site
Kaposvár, Hungary, 7400
GSK Investigational Site
Szeged, Hungary, 6720
Ireland
GSK Investigational Site
Cork, Ireland
GSK Investigational Site
Dublin, Ireland, 7
GSK Investigational Site
James Street, Ireland, 8
GSK Investigational Site
Limerick, Ireland
GSK Investigational Site
Tallaght, Dublin, Ireland, 24
GSK Investigational Site
Tullamore, Ireland
Israel
GSK Investigational Site
Beer-Sheva, Israel, 84101
GSK Investigational Site
Haifa, Israel, 31048
GSK Investigational Site
Haifa, Israel, 31096
GSK Investigational Site
Holon, Israel, 58100
GSK Investigational Site
Jerusalem, Israel, 91120
GSK Investigational Site
Petach-Tikva, Israel, 49100
GSK Investigational Site
Ramat Gan, Israel, 52621
GSK Investigational Site
Rehovot, Israel, 76100
GSK Investigational Site
Tel Aviv, Israel, 64239
Italy
GSK Investigational Site
Bologna, Emilia-Romagna, Italy, 40138
GSK Investigational Site
Brescia, Lombardia, Italy, 25123
GSK Investigational Site
Milano, Lombardia, Italy, 20162
GSK Investigational Site
Milano, Lombardia, Italy, 20122
GSK Investigational Site
Alessandria, Piemonte, Italy, 15100
GSK Investigational Site
Firenze, Toscana, Italy, 50134
Korea, Republic of
GSK Investigational Site
Hwasun, Korea, Republic of, 519-809
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
Mexico
GSK Investigational Site
Monterrey, Nuevo León, Mexico, 64460
GSK Investigational Site
Chihuahua, Mexico, 31203
GSK Investigational Site
Mexico City, Mexico, CP 14080
GSK Investigational Site
Oaxaca, Mexico, 68000
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1081 HV
Poland
GSK Investigational Site
Chorzow, Poland, 41-500
GSK Investigational Site
Torun, Poland, 87-100
GSK Investigational Site
Warszawa, Poland, 02-097
Puerto Rico
GSK Investigational Site
San Juan, Puerto Rico, 00927
Russian Federation
GSK Investigational Site
Nizhniy Novgorod, Russian Federation, 603126
GSK Investigational Site
Petrozavodsk, Russian Federation, 185019
GSK Investigational Site
St'Petersburg, Russian Federation, 191024
GSK Investigational Site
St'Petersburg, Russian Federation, 197341
GSK Investigational Site
St. Petersburg, Russian Federation, 197 089
Spain
GSK Investigational Site
Barcelona, Spain, 08036
GSK Investigational Site
Granada, Spain
GSK Investigational Site
Madrid, Spain, 28034
GSK Investigational Site
Málaga, Spain, 29010
GSK Investigational Site
Pozuelo de Alarcón/Madrid, Spain, 28223
GSK Investigational Site
Salamanca, Spain, 37007
GSK Investigational Site
Santander, Spain, 39008
Taiwan
GSK Investigational Site
Kaohsiung, Taiwan, 833
GSK Investigational Site
Tainan County, Taiwan, 736
GSK Investigational Site
Taoyuan, Taiwan, 333
Thailand
GSK Investigational Site
Bangkok, Thailand, 10330
GSK Investigational Site
Bangkok, Thailand, 10400
GSK Investigational Site
Bangkok, Thailand, 10700
GSK Investigational Site
Khon Kaen, Thailand, 40002
GSK Investigational Site
Songkla, Thailand, 90110
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: April 16, 2015
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
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Korea: Food and Drug Administration
Mexico: Secretaría de Salud
Taiwan: Food and Drug Administration, Department of Health, Executive Yuan
Greece: National Organization of Medicines
Hungary: National Institute of Pharmacy
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
Italy: Ministry of Health
Hong Kong: Department of Health
Israel: State of Israel Ministry of Health, Health Technology and Infrastructure Administration, Medical Devices Department
Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
Belgium: Federaal Agentschap voor Geneesmiddelen en Gezondheidsproducten
Russian Federation: Ministry of Health and social development of Russian Federation, Federal
Brazil: Agência Nacional de Vigilância Sanitária (ANVISA)
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
India: Drugs Controller General of India (DCGI)
Czech Republic: State Institute for Drug Control

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

ClinicalTrials.gov processed this record on September 02, 2015