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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01440374
First received: September 15, 2011
Last updated: May 2, 2017
Last verified: May 2017
Results First Received: March 10, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Participant, Care Provider, Investigator, Outcomes Assessor;   Primary Purpose: Supportive Care
Condition: Thrombocytopaenia
Interventions: Drug: eltrombopag
Drug: placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

Part 1, 17 subjects received open-label eltrombopag. Part 2, 145 subjects were randomized to receive eltrombopag plus SOC (N=98) or placebo plus SOC (N=47).

Part 3, 59 subjects from Part 2 entered Part 3. SOC was allowed as needed throughout the study. Subjects could receive disease-modifying therapy as needed.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and Grade 4 thrombocytopenia due to bone marrow insufficiency and had at least one of the following: platelet count <10 Giga cells per liter, platelet transfusion or symptomatic hemorrhagic event during the 4 weeks prior to enrollment, were enrolled in the study.

Reporting Groups
  Description
Part 1: Eltrombopag The eltrombopag starting dose the participants received was 100 milligrams (mg) daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks.
Part 2: Placebo Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study.
Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study.
Part 3: Eltrombopag

23 subjects of the 47 randomized to the placebo group in Part 2 entered part 3. 36 subjects of the 98 randomized to the Etrombopag group in Part 2 entered part 3.

All subjects received eltrombopag. Part 3 subjects could also have received treatment for their disease per local SOC, including azacitidine, decitabine, lenalidomide, and chemotherapy. The duration of Part 3 was to be 10 months for subjects from Part 1and 9 months for subjects from Part 2.


Participant Flow for 3 periods

Period 1:   Part 1: Open-label Phase
    Part 1: Eltrombopag   Part 2: Placebo   Part 2: Eltrombopag   Part 3: Eltrombopag
STARTED   17   0   0   0 
COMPLETED   11   0   0   0 
NOT COMPLETED   6   0   0   0 
Adverse Event                5                0                0                0 
Physician Decision                1                0                0                0 

Period 2:   Part 2; Double-blind Phase
    Part 1: Eltrombopag   Part 2: Placebo   Part 2: Eltrombopag   Part 3: Eltrombopag
STARTED   0   47   98   0 
COMPLETED   0   27   43   0 
NOT COMPLETED   0   20   55   0 
Physician Decision                0                8                17                0 
Withdrawal by Subject                0                4                5                0 
Protocol Violation                0                0                1                0 
Lack of Efficacy                0                1                0                0 
Adverse Event                0                7                31                0 
Not treated                0                0                1                0 

Period 3:   Part 3: Extension
    Part 1: Eltrombopag   Part 2: Placebo   Part 2: Eltrombopag   Part 3: Eltrombopag
STARTED   0   0   0   59 
COMPLETED   0   0   0   27 
NOT COMPLETED   0   0   0   32 
Withdrawal by Subject                0                0                0                5 
Adverse Event                0                0                0                13 
Physician Decision                0                0                0                14 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Part 3, 59 subjects from Part 2 entered Part 3 (23 of 47 subjects in the placebo group in Part 2 and 36 of 98 subjects in the eltrombopag group in Part 2). All subjects who entered Part 3 received treatment with eltrombopag. SOC was allowed as needed throughout the study. Subjects could receive disease-modifying therapy as needed.

Reporting Groups
  Description
Part 1: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. After all participants finished the 8 week treatment period, platelet response and safety were analyzed before initiating Part 2 of the study. Supportive standard of care was allowed as needed. The duration of Part 1 was 8 weeks.
Part 2: Placebo Participants received eltrombopag matching placebo once daily (3 tablets). Supportive standard of care was allowed as needed throughout the study.
Part 2: Eltrombopag The eltrombopag starting dose the participants received was 100 mg daily (50 mg for participants of East Asian heritage). The duration of treatment with the initial dose level prior to first dose escalation was determined based on the platelet response and toxicity observed in Part 1. The dose of eltrombopag was escalated from 100 mg to 200 mg (50 mg to 100 mg for East Asians) and further from 200 mg to 300 mg once daily (100 mg to 150 mg for East Asians) based on the platelet response and safety data after two weeks of current dose level. Supportive standard of care was allowed as needed throughout the study.
Total Total of all reporting groups

Baseline Measures
   Part 1: Eltrombopag   Part 2: Placebo   Part 2: Eltrombopag   Total 
Overall Participants Analyzed 
[Units: Participants]
 17   47   98   162 
Age 
[Units: Years]
Mean (Standard Deviation)
 71.5  (10.78)   70.6  (10.72)   72.3  (8.94)   71.8  (9.56) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      7  41.2%      16  34.0%      32  32.7%      55  34.0% 
Male      10  58.8%      31  66.0%      66  67.3%      107  66.0% 
Race/Ethnicity, Customized 
[Units: Participants]
       
African American/African Heritage   0   0   1   1 
Asian - East Asian Heritage   3   5   9   17 
Asian - South East Asian Heritage   0   2   2   4 
White - Arabic/North African Heritage   0   1   5   6 
White - White/Caucasian/European Heritage   14   39   81   134 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Platelet Response up to Week 8 During Part 1   [ Time Frame: From Baseline up to Week 8 during Part 1 ]

2.  Primary:   Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2   [ Time Frame: From Week 5 up to Week 12 during Part 2 ]

3.  Secondary:   Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects)   [ Time Frame: Day 1 to week 8 ]

4.  Secondary:   Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)   [ Time Frame: Day 1 to week 12 ]

5.  Secondary:   Mean Number of Platelet Transfusions   [ Time Frame: Weeks 5 to 12 ]

6.  Secondary:   Hematologic Improvement   [ Time Frame: Weeks 5 to 12 ]

7.  Secondary:   Change in Mean Platelet Count   [ Time Frame: Baseline to Week 12 ]

8.  Secondary:   Maximum Duration of Platelet Transfusion Independence   [ Time Frame: Weeks 5 to 12 ]

9.  Secondary:   Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale   [ Time Frame: Weeks 5 to 12 ]

10.  Secondary:   Independent Reviewer-Assessed Best Response   [ Time Frame: up to week 12 ]

11.  Secondary:   Independent Reviewer Assessed Disease Progression   [ Time Frame: Up to week 12 ]

12.  Secondary:   Median Overall Survival   [ Time Frame: Up to 13 months ]

13.  Secondary:   Summary of Health Outcomes   [ Time Frame: week 12 ]

14.  Secondary:   Functional Assessment of Cancer Therapy (FACT)   [ Time Frame: Change from baseline, up to week 12 ]

15.  Secondary:   EQ-5D Utility Score Analysis   [ Time Frame: Change from baseline, up to week 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01440374     History of Changes
Other Study ID Numbers: 114968
2011-000114-19 ( EudraCT Number )
Study First Received: September 15, 2011
Results First Received: March 10, 2016
Last Updated: May 2, 2017