Open-label Study to Evaluate the Safety, PK, and PD of MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias
MEK111759 is a dose-escalation, Phase I/II, open-label study to determine the recommended dose and regimen for the orally administered MEK inhibitor GSK1120212 in subjects with relapsed or refractory leukemias. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles. This study will identify the maximum tolerated and recommended Phase II doses using a dose-escalation procedure. Dose escalations will continue based on predefined parameters until a maximum tolerated dose is established. In Phase II, the clinical efficacy of GSK1120212 in subjects with relapsed or refractory leukaemias (AML, MDS or CMML) will be determined.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Dose-Escalation, Phase I/II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of the MEK Inhibitor GSK1120212 in Subjects With Relapsed or Refractory Leukemias|
- Phase I: AEs and changes in laboratory values [ Time Frame: Until a subject has a Dose Limiting Toxicity, withdraws from the study or dies ] [ Designated as safety issue: Yes ]
- Phase II: Clinical Response per protocol. [ Time Frame: Until a subject withdraws, approximatley 12 months, or dies ] [ Designated as safety issue: No ]
- Phase I: PK and PD markers per protocol [ Time Frame: Until a subject has a Dose Limiting Toxicity, withdraws from the study or dies ] [ Designated as safety issue: No ]
- Phase II: PK parameters per protocol [ Time Frame: Until a subject withdraws, approximatley 12 months or dies ] [ Designated as safety issue: No ]
|Study Start Date:||May 2011|
|Study Completion Date:||April 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Experimental: Phase I
The proposed treatment schedule of GSK1120212 is continuous daily dosing. At the initiation of dosing, a loading dose will be given prior to starting continuous dosing (maintenance dose).
Alterations to the dose and schedule will be based on emerging PK, PD, and tolerability data. The goal will be to define a regimen that is well tolerated and provides adequate PK and PD. This will be the recommended Phase II schedule.
Starting dose based on GSK protocol MEK111054 and then dose escalation based on Dose Limiting Toxicities per protocol.
Experimental: Phase II
A dose determined by Phase I to further evaulate the safety profile, PK, PD, and clinical activity of GSK1120212.
Dose will be maximum tolerated dose based on Phase I results.
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|Study Director:||GSK Clinical Trials||GlaxoSmithKline|