Clinical Trial: Growth Factor Signature (GFS) Pilot Study (MK0000-098)(COMPLETED)

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Multicenter Phase Ib Trial to Determine Whether a Gene Expression Signature Changes in Response to Treatment With Bcr-Abl Inhibitors in Patients With Blast Phase Philadelphia C

Brief Summary: This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors.

Detailed Summary:
Sponsor: Merck Sharp & Dohme Corp.

Current Primary Outcome:

• Growth Factor Signature (GFS) Variability at Baseline [ Time Frame: Screening to Day 1 Predose ]

  The GFS was measured by microarray analysis using the entire 101 gene signature. The GFS is quantified as the change in gene expression between two separate samples collected from the same patient. The signature has 101 genes in two oppositely regulated arms, which are pre-specified. The expression of genes in the UP arm goes up with increasing pathway activity, and the expression of genes in the DOWN arm goes down with increasing pathway activity.

  The GFS variability was represented by the GFS change between two baseline samples (Mean GFS Fold Ratio [Screening to Day 1 Predose]).

• Growth Factor Signature (GFS) Change From Baseline Measured by Time Weighted Average (TWA) for Days 1 to 22 [ Time Frame: Baseline to 22 Days After Initiation of Therapy ]

  The GFS was measured by microarray analysis using the entire 101 gene signature.

  The TWA is the area under the curve (AUC) divided by the time interval (for this study it was the AUC of gene-expression divided by Days 1 to 22).

  Participants with blast phase Ph+ CML or Ph+ ALL were measured for change in the GFS post-treatment when treated with imatinib, dasatinib, or nilotinib, using Microarray. Change was represented as the GFS Fold Ratio of TWA for Days 1 to 22 to Baseline.

Original Primary Outcome: The change in the gene expression signature (GFS) before and after treatment will be measured to determine whether a change or lack of change predicts response or resistance [ Time Frame: 4 months ]

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Merck Sharp & Dohme Corp.

Dates:
Date Received: March 5, 2009
Date Started: June 2009
Date Completion:
Last Updated: September 28, 2015
Last Verified: September 2015