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

Thrombocytopaenia Clinical Trial

— ASPIRE  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01440374
• Other study ID #: 114968
• Status: Active, not recruiting
• Phase: Phase 2
• First received: September 15, 2011
• Last updated: April 16, 2015
• Start date: September 2011
• Est. completion date: January 2016

Study information

• Verified date: April 2015
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Espanola de Medicamentos y Productos SanitariosNetherlands: Centrale Commissie Mensgesbonden Onderzoek (Central Committee on Research Involving Human Subjects) Den Haag (The Hague), The NetherlandsUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyKorea: Food and Drug AdministrationMexico: Secretaría de SaludTaiwan: Food and Drug Administration, Department of Health, Executive YuanGreece: National Organization of MedicinesHungary: National Institute of PharmacyThailand: Food and Drug AdministrationUnited States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaThailand: Ministry of Public HealthItaly: Ministry of HealthHong Kong: Department of HealthIsrael: State of Israel Ministry of Health, Health Technology and Infrastructure Administration, Medical Devices DepartmentPoland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBKGermany: Bundesinstitut für Arzneimittel und MedizinprodukteBelgium: Federaal Agentschap voor Geneesmiddelen en GezondheidsproductenRussian Federation: Ministry of Health and social development of Russian Federation, FederalBrazil: Agência Nacional de Vigilância Sanitária (ANVISA)Peru: General Directorate of Pharmaceuticals, Devices, and DrugsIndia: Drugs Controller General of India (DCGI)Czech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 163
• Est. completion date: January 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ß-human chorionic gonadotropin [ß-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.

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

Related Conditions & MeSH terms

• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Thrombocytopaenia
• Thrombocytopenia
• Thrombocytosis

Intervention

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)
• 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)

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Belgium	GSK Investigational Site	Antwerpen
Belgium	GSK Investigational Site	Brasschaat
Belgium	GSK Investigational Site	Brugge
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Gent
Belgium	GSK Investigational Site	Leuven
Belgium	GSK Investigational Site	Yvoir
Brazil	GSK Investigational Site	Barretos	São Paulo
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Goiânia - GO	Goiás
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Rio de Janeiro
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Halifax	Nova Scotia
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Praha
Czech Republic	GSK Investigational Site	Praha 10
Czech Republic	GSK Investigational Site	Praha 2
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Mannheim	Baden-Wuerttemberg
Germany	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Heraklion, Crete
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Thessaloniki
Hong Kong	GSK Investigational Site	Chai Wan
Hong Kong	GSK Investigational Site	Shatin, New Territories
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Kaposvár
Hungary	GSK Investigational Site	Szeged
Ireland	GSK Investigational Site	Cork
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	James Street
Ireland	GSK Investigational Site	Limerick
Ireland	GSK Investigational Site	Tallaght, Dublin
Ireland	GSK Investigational Site	Tullamore
Israel	GSK Investigational Site	Beer-Sheva
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Petach-Tikva
Israel	GSK Investigational Site	Ramat Gan
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel Aviv
Italy	GSK Investigational Site	Alessandria	Piemonte
Italy	GSK Investigational Site	Bologna	Emilia-Romagna
Italy	GSK Investigational Site	Brescia	Lombardia
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Korea, Republic of	GSK Investigational Site	Hwasun
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Oaxaca
Netherlands	GSK Investigational Site	Amsterdam
Poland	GSK Investigational Site	Chorzow
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Warszawa
Puerto Rico	GSK Investigational Site	San Juan
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Petrozavodsk
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Pozuelo de Alarcón/Madrid
Spain	GSK Investigational Site	Salamanca
Spain	GSK Investigational Site	Santander
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Tainan County
Taiwan	GSK Investigational Site	Taoyuan
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Songkla
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Bornx	New York
United States	GSK Investigational Site	Boston	Massachusetts
United States	GSK Investigational Site	Hackensack	New Jersey
United States	GSK Investigational Site	Hot Springs	Arkansas
United States	GSK Investigational Site	Jacksonville	Florida
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Kansas City	Missouri
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Milwaukee	Wisconsin
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Stanford	California
United States	GSK Investigational Site	Voorhees	New Jersey
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in clinically relevant thrombocytopenic events		weeks 5-12	No
Secondary	Hematologic improvement (change in platelets, neutrophils and hemoglobin)		baseline and weekly for 3 months	No
Secondary	Assessment of platelet counts		3 months	No
Secondary	Need for platlet transfusions		3 months	No
Secondary	Duration of platelet transfusion-independence		3 months	No
Secondary	The occurrence and severity of bleeding, measured using the WHO Bleeding Scale		3 months	No
Secondary	Disease response		3 months	No
Secondary	Safety as measured by number of adverse events.		3 months	No
Secondary	Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage		3 months	No
Secondary	FACT-TH-18 and the EQ-5D Questionnaires		3 months	No
Secondary	Disease progression		3 months	No
Secondary	Evaluate MDS and AML disease response		3 months	No
Secondary	Evaluate MDS and AML disease progression		3 months	No
Secondary	Evaluate overall survival		3 months	No