Open-label Study to Evaluate the Safety, PK, and PD of MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00920140
First received: June 12, 2009
Last updated: March 6, 2014
Last verified: March 2014
Results First Received: November 21, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Cancer
Intervention: Drug: GSK1120212

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This is a Phase I/II study. Phase I is a dose escalation phase in participants with relapsed or refractory leukaemias to identify the recommended dose of GSK1120212 for Phase II. Phase II further evaluates the safety and efficacy of the recommended dose.

Reporting Groups
  Description
GSK1120212 < 2 mg OD Participants with relapsed or refractory leukemias received either GSK1120212 3 milligrams (mg) loading dose (LD) followed by 1 mg once daily (OD) (3/1 mg LD/OD), or 1 mg OD as a continuous dose.
GSK1120212 2 mg OD Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose.
Cohort 1: AML/MDS With RAS Mutation Participants with relapsed or refractory acute myeloid leukemia (AML) or myelodysplasia (MDS) with rat sarcoma (RAS) mutation received GSK1120212 2 mg OD as a continuous dose.
Cohort 2: AML/MDS/CMML With RAS wt/Unknown Participants with relapsed or refractory AML or MDS or chronic myelomonocytic leukemia (CMML) with RAS wild type (wt) or unknown mutation received GSK1120212 2 mg OD as a continuous dose.
Cohort 3: CMML With RAS Mutation Participants with relapsed or refractory CMML with RAS mutation received GSK1120212 2 mg OD as a continuous dose.

Participant Flow for 2 periods

Period 1:   Phase 1 (Dose Escalation)
    GSK1120212 < 2 mg OD     GSK1120212 2 mg OD     Cohort 1: AML/MDS With RAS Mutation     Cohort 2: AML/MDS/CMML With RAS wt/Unknown     Cohort 3: CMML With RAS Mutation  
STARTED     5     9     0     0     0  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     5     9     0     0     0  
Adverse Event                 3                 3                 0                 0                 0  
Lack of Efficacy                 2                 4                 0                 0                 0  
Withdrawal by Subject                 0                 2                 0                 0                 0  

Period 2:   Phase 2
    GSK1120212 < 2 mg OD     GSK1120212 2 mg OD     Cohort 1: AML/MDS With RAS Mutation     Cohort 2: AML/MDS/CMML With RAS wt/Unknown     Cohort 3: CMML With RAS Mutation  
STARTED     0     0     50     22     11  
COMPLETED     0     0     0     0     0  
NOT COMPLETED     0     0     50     22     11  
Adverse Event                 0                 0                 14                 2                 3  
Lack of Efficacy                 0                 0                 29                 14                 5  
Lost to Follow-up                 0                 0                 0                 1                 0  
Physician Decision                 0                 0                 3                 3                 2  
Withdrawal by Subject                 0                 0                 4                 2                 1  



  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.
No text entered.

Reporting Groups
  Description
GSK1120212 <2 mg OD Participants with relapsed or refractory leukemias received either GSK1120212 3 milligrams (mg) loading dose (LD) followed by 1 mg once daily (OD) (3/1 mg LD/OD), or 1 mg OD as a continuous dose.
GSK1120212 2 mg OD Participants with relapsed or refractory leukemias received GSK1120212 2 mg OD as a continuous dose.
Cohort 1: AML/MDS With RAS Mutation Participants with relapsed or refractory AML or MDS with RAS mutation received GSK1120212 2 mg OD as a continuous dose.
Cohort 2: AML/MDS/CMML With RAS wt/Unknown Participants with relapsed or refractory AML or MDS or CMML with RAS wt or unknown mutation received GSK1120212 2 mg OD as a continuous dose.
Cohort 3: CMML With RAS Mutation Participants with relapsed or refractory CMML with RAS mutation received GSK1120212 2 mg OD as a continuous dose.
Total Total of all reporting groups

Baseline Measures
    GSK1120212 <2 mg OD     GSK1120212 2 mg OD     Cohort 1: AML/MDS With RAS Mutation     Cohort 2: AML/MDS/CMML With RAS wt/Unknown     Cohort 3: CMML With RAS Mutation     Total  
Number of Participants  
[units: participants]
  5     9     50     22     11     97  
Age  
[units: Years]
Mean ± Standard Deviation
  70.4  ± 15.71     60.2  ± 15.86     65.6  ± 10.71     59.6  ± 18.89     67.7  ± 6.87     64.2  ± 13.69  
Gender  
[units: Participants]
           
Female     4     2     22     7     6     41  
Male     1     7     28     15     5     56  
Race/Ethnicity, Customized  
[units: Participants]
           
African American/African Heritage     1     0     5     2     0     8  
White - White/Caucasian/European Heritage     4     9     40     18     9     80  
Asian - Central/South Asian Heritage     0     0     0     1     1     2  
Asian - Japanese Heritage     0     0     1     0     0     1  
Asian - South East Asian Heritage     0     0     0     1     0     1  
Missing     0     0     4     0     1     5  



  Outcome Measures
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1.  Primary:   Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

2.  Primary:   Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Hematology Parameters by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

3.  Primary:   Number of Participants With a Change From Baseline Grade to Grade 3 and 4 for the Indicated Clinical Chemistry Parameters by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

4.  Primary:   Number of Participants With a Change From Baseline in Heart Rate by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

5.  Primary:   Number of Participants With a Change From Baseline in Systolic and Diastolic Blood Pressure by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

6.  Primary:   Number of Participants With a Change From Baseline in Temperature by Dose   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

7.  Primary:   Number of Participants With an Investigator-assessed Best Response (Achieving Complete Response [CR], Marrow CR, Partial Response [PR], Complete Response Without Platelet Recovery [CRp] or Morphologic Leukaemia-free State[MLFS]) by Cohort   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days) ]

8.  Secondary:   AUC(0-24), AUC(0-t), and AUC(0-tau) of GSK1120212 in Part 1   [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 ]

9.  Secondary:   Cmin and Cmax of GSK1120212 in Part 1   [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 ]

10.  Secondary:   t1/2 at C1D1 and t1/2 Effective (Eff.) at C1D15 of GSK1120212 in Part 1   [ Time Frame: Cycle 1 Day 1 (t1/2) and Cycle 1 Day 15 (t1/2eff) ]

11.  Secondary:   Tmax of GSK1120212 in Part 1   [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 ]

12.  Secondary:   Accumulation Ratio (AR) of GSK1120212 in Part 1   [ Time Frame: Cycle 1 Day 1 and Cycle 1 Day 15 ]

13.  Secondary:   Ctau of GSK1120212 in Part 2   [ Time Frame: C1D15, C2D1, C3D1, C4D1, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1 and C12D1 ]

14.  Secondary:   Overall Survival by Cohort   [ Time Frame: From the start of the study drug until the final study visit (up to approximately 407 days ) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00920140     History of Changes
Other Study ID Numbers: 111759
Study First Received: June 12, 2009
Results First Received: November 21, 2013
Last Updated: March 6, 2014
Health Authority: United States: Food and Drug Administration