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CTRI Number  CTRI/2012/08/002911 [Registered on: 24/08/2012] Trial Registered Prospectively
Last Modified On: 16/07/2013
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group, Placebo Controlled Trial 
Public Title of Study   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 myelodysplastic syndromes and acute myeloid leukemia. 
Scientific Title of Study   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 
Trial Acronym  ASPIRE 
Secondary IDs if Any  
Secondary ID  Identifier 
2010N109350_02 dated 25 May 2012  Protocol Number 
NCT01440374  ClinicalTrials.gov 
TRC114968  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name   
Designation   
Affiliation   
Address 




 
Phone    
Fax    
Email    
 
Details of Contact Person
Scientific Query  
Name  Dr Jeroze Dalal 
Designation  General Manager 
Affiliation  GlaxoSmithKline Pharmaceuticals Limited 
Address  252, Dr. A.B. Road, Worli Mumbai MAHARASHTRA 400030 India Mumbai MAHARASHTRA 400030 India

Mumbai
MAHARASHTRA
400030
India 
Phone  91-22-2495395  
Fax  91-22-24947415  
Email  jeroze.j.dalal@gsk.com  
 
Details of Contact Person
Public Query  
Name  Kedar Nayak 
Designation  Clinical Research Manager 
Affiliation  GlaxoSmithKline Pharmaceuticals Limited 
Address  252, Dr. A.B. Road, Worli Mumbai MAHARASHTRA 400030 India Mumbai MAHARASHTRA 400030 India

Mumbai
MAHARASHTRA
400030
India 
Phone  91-22-2495365  
Fax  022-24947415  
Email  kedar.n.nayak@gsk.com  
 
Source of Monetary or Material Support  
GlaxoSmithKline Pharmaceuticals Ltd.  
 
Primary Sponsor  
Name  GlaxoSmithKline Pharmaceuticals Ltd  
Address  GlaxoSmithKline Pharmaceuticals Ltd. 252, Dr. A.B. Road, Mumbai 400030. India. 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Argentina
Belgium
Brazil
Canada
Czech Republic
France
Germany
Greece
Hong Kong
Hungary
India
Ireland
Israel
Italy
Mexico
Netherlands
Peru
Poland
Russian Federation
Spain
Taiwan
Thailand
United Kingdom
United States of America
Democratic People's Republic of Korea  
Sites of Study  
No of Sites = 9  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Soumya Bhattacharya  Apollo Gleneagles Hospital  58-Canal Circular Road, Sector 3, Salt lake, Kolkatta 700054
Kolkata
WEST BENGAL 		 91-033-23359676

rinku_soumva@hotmail.com 
DrJoseph John  Christian Medical College, Ludhiana  Clinical Haematology & Haemato-Oncology Unit, Hemato-Oncology and Bone Marrow Transplant Unit, Brown Road,Ludhiana 141008
Ludhiana
PUNJAB 		 9878659525

mjosephjohn@gmail.com 
Dr Biju George  Christian Medical College, Vellore   Department of Hematology IDA Scudder Road, Vellore 632004
Vellore
TAMIL NADU 		 91-416-2282352

biju@cmcvellore.ac.in 
Dr Satish A Kumar  Columbia Asia Hoapital  #26/1 Feet, Dr. Rajkumar Road, Malleshwaram West, Banglore 560055
Bangalore
KARNATAKA 		 9611195666

doctorstats@gmail.com 
Dr Samir Melinkeri  Deenanath Mangeshkar Hospital & Research Center  Department of Hematology, Erandawane, Pune 411004
Pune
MAHARASHTRA 		 9371608489

docmelinkeri@yahoo.com 
Dr Seema Bhatwadekar  Global Baroda Hospital  Department of Hematology Near Shreyas Vidhyalaya Manjalpur, Vadodra 390011
Vadodara
GUJARAT 		 9374511709

ssbkar16@gmail.com 
Dr Senthil Rajappa  Indo-American Cancer Hospital and Research Institute  Senior Consultant,Dept. Of Medical Oncology, Banjara Hills,Road No.14, Hyderabad 500034
Hyderabad
ANDHRA PRADESH 		 4023542120

siddharth142@sify.com 
Dr Vijay Ramanan  Jehangir Hospital  Jehangir Clinical Development Centre Pvt. Ltd., 32 Sassoon Road, Pune 411001
Pune
MAHARASHTRA 		 9325315471

mvijayr@gmail.com 
Dr Sandip Shah  Vendanta Instutute of Medical Sciences  Hemato-oncology Clinic, 1st Fllor, Near Samved Hospital, Commerce College Road, Navrangpura,Ahmedabad-380009
Ahmadabad
GUJARAT 		 9824041170

sandip60@yahoo.com 
 
Details of Ethics Committee  
No of Ethics Committees= 9  
Name of Committee  Approval Status 
Ethics Committe of CIMS, Ahmedabad  Approved 
Ethics Committee of Global Baroda Hospital, Vadodara  Submittted/Under Review 
Institutional Ethics Committee, Apollo GlenEagles Hospitals, Kolkata  Submittted/Under Review 
Institutional Ethics Committee, DMH & RC, Pune  Submittted/Under Review 
Institutional Ethics Committee, Indo American Cancer Institute & Research Centre, Hyderabad  Submittted/Under Review 
Institutional Ethics Committee, Ludhiana  Submittted/Under Review 
Institutional Review Board, Vellore  Submittted/Under Review 
Jehangir Clinical Development Center Institutional Review Board, Pune  Approved 
lnstitutional Ethics Committee Columbia Asia Hospitals, Bangalore  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Acute Myeloid Leukemia,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Eltrombopag  Oral administration Eltrombopag 100 mg once daily has been selected as the starting dose for this study. Subsequent dose adjustments will be dependent on each subject’s platelet counts. Total Duration of Therapy : 52 weeks. 
Comparator Agent  Placebo  Oral administration Placebo Tablets once daily Total Duration of Therapy : 52 weeks 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  55.00 Year(s)
Gender  Both 
Details  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 <25 Gi/L) due to
bone marrow insufficiency (or platelet count ≥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.
3. Subjects must have platelet count, bleeding and platelet transfusion data available
over a period of at least 4 weeks prior to randomization.
4. Prior systemic treatment for malignancy, with the exception of hydroxyurea (see
Section 6.1.2), 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.5. Subjects with a prior stem cell transplant (SCT) must have relapsed after the SCT.
6. Subjects must have stable disease (as defined by treatment guidelines and
investigator discretion) and, in the opinion of the investigator, must be expected to
complete a 12 week treatment period.
7. ECOG Status 0-2.
8. Subject must be able to understand and comply with protocol requirements and
instructions.
9. Subject has signed and dated an informed consent form.
10. 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 ≤ 2.5xULN11. Women must be either of non-child bearing potential (see Section 7.3.12.2.1, for
definition) or women with child-bearing potential and men with reproductive
potential must be willing to practice acceptable methods of birth control during the
study (See Section 7.3.12.2, for acceptable methods of birth control). Women of
childbearing potential must have a negative serum pregnancy test within 7 days prior
to the first dose of study treatment.
12. 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. 
 
ExclusionCriteria 
Details  1. Subjects with MDS and an IPSS of low or intermediate-1 risk.
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) at baseline.
5. Subjects with a palpable spleen must have a splenic ultrasound to confirm spleen
length is ≤16 cm. Subjects with palpable spleen 16 cm are not eligible.
6. Leukocytosis ≥25,000/uL on Day 1 of treatment with study medication.
7. 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.
8. 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.
9. Current alcohol or drug abuse.
10. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
longer) preceding the first dose of study medication.
11. Active and uncontrolled infections (e.g. sepsis).
12. Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).
13. Subjects with liver cirrhosis (as determined by the investigator).
14. Subjects receiving or planned to receive any prohibited medication (see Section 6.2).15. 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.
16. In France, subjects who have participated in any study using an investigational drug
during the previous 30 days. 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Investigator Blinded 
Primary Outcome  
Outcome  TimePoints 
The primary objective of this study is to determine the reduction in the number of clinically relevant thrombocytopenic events (CRTE) in subjects with MDS or AML who have Grade 4 thrombocytopenia and are treated with eltrombopag compared to those treated with placebo.   The primary endpoint is clinically relevant thrombocytopenic events (CRTE) during weeks 5-12 of treatment.  
 
Secondary Outcome  
Outcome  TimePoints 
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
 		 Number of platelet transfusions
Hematologic improvement (platelets, neutrophils and hemoglobin)
Assessment of platelet counts throughout the study
 
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 response
To evaluate MDS and AML disease progression
 		 Duration of platelet transfusion-independence.
The occurrence and severity of bleeding, measured using the WHO Bleeding Scale.
Disease response
Disease progression
 
To evaluate overall survival
To evaluate the safety and tolerability of eltrombopag.
To evaluate the effect of eltrombopag on medical resource utilization.
To evaluate the effect of eltrombopag on health related quality of life.
 		 Overall survival
Physical exam findings, clinical monitoring, vital signs, clinical laboratory tests, and adverse event reporting (including hemorrhagic and transfusion-related adverse events).
Medical resource utilization, including specifically due to thrombocytopenia and hemorrhage.
FACT-TH-18 and the EQ-5D
 
Secondary objectives compare the following in subjects treated with eltrombopag and placebo:  Secondary endpoints compare the following in subjects treated with eltrombopag and placebo: 
 
Target Sample Size   Total Sample Size="140"
Sample Size from India="20" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2 
Date of First Enrollment (India)   31/10/2012 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  30/09/2011 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="2"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  		 Open to Recruitment 
Recruitment Status of Trial (India)  Other (Terminated) 
Publication Details    
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Thrombocytopenia is a significant problem for patients with malignancies and can be life-threatening.  The etiology of thrombocytopenia depends on the specific type and location of the malignancy, and may encompass an autoimmune component, the presence of splenomegaly and/or prior and current treatments. 

In myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), megakaryopoiesis can be impaired in both a quantitative (lack of megakaryocytes), and qualitative way (increased apoptosis in megakaryocytes from patients with MDS).  Interestingly, increased apoptosis of megakaryocytes has also been observed in idiopathic thrombocytopenic purpura (ITP) [Houwerzijl, 2005].  Based on the pathophysiology of thrombocytopenia in MDS and AML and based on eltrombopag’s known mechanism of action, it is very likely that eltrombopag will be able to increase platelet counts and reduce thrombocytopenic sequelae (platelet transfusions and haemorrhages) in patients with MDS and AML.

 

 
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