Treatment of Low Platelet Counts Due to advanced Myelodysplastic Syndrome or Acute Myeloid Leukemia with Eltrombopag

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). ASPIRE: A Study of EltromboPag In Myelodysplastic SyndRomes and AcutE Myeloid Leukemia - PhII study in platelet transfusion dependent pts

Status

Active, not recruiting

Phases

Unknown

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2011-000114-19-BE

Enrollment

160

Registered

2011-08-09

Start date

2011-11-29

Completion date

Unknown

Last updated

2016-03-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Thrombocytopenic Subjects with advanced Myelodysplastic Syndromes or Acute Myeloid Leukemia MedDRA version: 17.0 Level: LLT Classification code 10060356 Term: Acute myeloid leukaemia without mention of remission System Organ Class: 100000004864 MedDRA version: 17.0 Level: LLT Classification code 10028534 Term: Myelodysplastic syndrome NOS System Organ Class: 100000004864

Interventions

Product Name: Eltrombopag Product Code: SB-497115 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: ELTROMBOPAG CAS Number: 496775-61-2 Current Sponsor code: SB-497115 Concentration unit: m

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. 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. 2. Subjects must have Grade 4 thrombocytopenia (platelet counts =65 years) yes F.1.3.1 Number of subjects for this age range 135

Exclusion criteria

Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Subjects with MDS and an IPSS of low or intermediate-1 risk at screening. 2. Subjects with a diagnosis of acute promyelocytic or megakaryocytic leukemia or AML secondary to a myeloproliferative neoplasm. 3. History of treatment with romiplostim or other TPO-R agonists. 4. Subjects with a QTc >480 msec (QTc >510 msec for subjects with Bundle Branch Block). 5. Leukocytosis =25,000/uL on Day 1 of treatment with study medication. 6. 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. 7. 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. 8. Current alcohol or drug abuse. 9. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication. 10. Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C). 11. Subjects infected Human Immunodeficiency Virus (HIV). 12. Subjects with liver cirrhosis (as determined by the investigator). 13. Subjects receiving or planned to receive any prohibited medication (see Section 6.2). 14. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidine, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects’ participation. 15. In France, subjects who have participated in any study using an investigational drug during the previous 30 days.

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: Screening, Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 11, End of Therapy – Week 12, Early Withdrawal Visit, Follow up Visit – Week 1, 2, 3 & 4;Primary end point(s): Part 2 of Study: The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment. CRTE are defined as: • platelet counts <10 Gi/L, or • platelet transfusions, or • =Grade 3 hemorrhagic adverse events.;Main Objective: Part 1 open-label, 8 week first part of the study are: • To evaluate the safety and tolerability of eltrombopag. • To determine optimal dose escalation scheme for use in Part 2 of the study by assessing the dose of eltrombopag required to achieve platelet count response. • To characterize plasma eltrombopag pharmacokinetics (steady-state plasma eltrombopag Cmax, tmax, AUC(0-t), CL/F, and half-life). Part 2: • The primary objective of this study is to determine reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia (<25 Gi/L) and are treated with eltrombopag compared to those treated with placebo. Part 3: The objectives of Part 3 of the study are to evaluate the long-term durability of clinical benefit as well as overall survival, the long-term safety and tolerability of eltrombopag in subjects with MDS and AML.” ;Secondary Objective: Secondary objectives compare the following in subjects treated with eltrombopag and placebo: • To evaluate the effect of eltrombopag on the need for platelet transfusions. • To evaluate hematologic improvement • To evaluate the effect of eltrombopag on platelet counts • To evaluate the effect of eltrombopag on the duration of platelet transfusion independence. • To evaluate the effect of eltrombopag on bleeding symptoms. • To evaluate MDS and AML disease ressponse • To evaluate MDS and AML disease progression • To evaluate overall survival • To evaluate the safety and tolerability of e	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: Screening, Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 11, End of Therapy – Week 12, Early Withdrawal Visit, Follow up Visit – Week 1, 2, 3 & 4;Primary end point(s): Part 2 of Study: The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment. CRTE are defined as: • platelet counts <10 Gi/L, or • platelet transfusions, or • =Grade 3 hemorrhagic adverse events.;Main Objective: Part 1 open-label, 8 week first part of the study are: • To evaluate the safety and tolerability of eltrombopag. • To determine optimal dose escalation scheme for use in Part 2 of the study by assessing the dose of eltrombopag required to achieve platelet count response. • To characterize plasma eltrombopag pharmacokinetics (steady-state plasma eltrombopag Cmax, tmax, AUC(0-t), CL/F, and half-life). Part 2: • The primary objective of this study is to determine reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia (<25 Gi/L) and are treated with eltrombopag compared to those treated with placebo. Part 3: The objectives of Part 3 of the study are to evaluate the long-term durability of clinical benefit as well as overall survival, the long-term safety and tolerability of eltrombopag in subjects with MDS and AML.” ;Secondary Objective: Secondary objectives compare the following in subjects treated with eltrombopag and placebo: • To evaluate the effect of eltrombopag on the need for platelet transfusions. • To evaluate hematologic improvement • To evaluate the effect of eltrombopag on platelet counts • To evaluate the effect of eltrombopag on the duration of platelet transfusion independence. • To evaluate the effect of eltrombopag on bleeding symptoms. • To evaluate MDS and AML disease ressponse • To evaluate MDS and AML disease progression • To evaluate overall survival • To evaluate the safety and tolerability of e

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: Screening, Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 11, End of Therapy – Week 12, Early Withdrawal Visit, Follow Up Visits – Week 1, 2, 3 & 4;Secondary end point(s): Secondary endpoints compare the following in subjects treated with eltrombopag and placebo: • Number of platelet transfusions • Hematologic improvement (platelets, neutrophils and hemoglobin) • Assessment of platelet counts throughout the study • Duration of platelet transfusion-independence. • The occurrence and severity of bleeding, measured using the WHO Bleeding Scale. • Disease response • Disease progression • Overall survival • Physical exam findings, clinical monitoring, vital signs, clinical laboratory tests, and adverse event reporting (including hemorrhagic and transfusionrelated adverse events). • Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage. • FACT-TH-18 and the EQ-5D •Population pharmacokinetic parameters, including evaluation of covariates (combined data from Parts 1 and 2). Relationships between exposure and pharmacodynamic response will also be evaluated as appropriate.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: Screening, Baseline, Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 11, End of Therapy – Week 12, Early Withdrawal Visit, Follow Up Visits – Week 1, 2, 3 & 4;Secondary end point(s): Secondary endpoints compare the following in subjects treated with eltrombopag and placebo: • Number of platelet transfusions • Hematologic improvement (platelets, neutrophils and hemoglobin) • Assessment of platelet counts throughout the study • Duration of platelet transfusion-independence. • The occurrence and severity of bleeding, measured using the WHO Bleeding Scale. • Disease response • Disease progression • Overall survival • Physical exam findings, clinical monitoring, vital signs, clinical laboratory tests, and adverse event reporting (including hemorrhagic and transfusionrelated adverse events). • Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage. • FACT-TH-18 and the EQ-5D •Population pharmacokinetic parameters, including evaluation of covariates (combined data from Parts 1 and 2). Relationships between exposure and pharmacodynamic response will also be evaluated as appropriate.

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Countries

Argentina, Belgium, Brazil, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, India, Ireland, Israel, Italy, Korea, Republic of, Netherlands, Peru, Poland, Russian Federation, Spain, Taiwan, Thailand, United Kingdom, United States

Contacts

Public ContactClinical Trials Helpdesk

GlaxoSmithKline Research & Development

GSKClinicalSupportHD@gsk.com+442089904466

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026