Trial Outcomes & Findings for Growth Factor Signature (GFS) Pilot Study (MK0000-098)(COMPLETED) (NCT NCT00860535)

Results Overview

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 \[Screening to Day 1 Predose\]).

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

Screening to Day 1 Predose

Results posted on

2015-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Ph+ CML or Ph+ ALL Participants with blast phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML) or Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL) who were beginning treatment with imatinib, dasatinib or nilotinib as per standard of care. All participants who had evaluable gene expression data were included in the analysis.
Overall Study STARTED	9
Overall Study DISCONTINUED	1
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ph+ CML or Ph+ ALL n=9 Participants Growth Factor Signature (GFS) biomarker evaluation in participants with blast phase Ph+ CML or Ph+ ALL who were treated with imatinib, dasatinib or nilotinib as per standard of care.
Age, Continuous	48.0 years STANDARD_DEVIATION 15.3 • n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	6 Participants n=99 Participants

PRIMARY outcome

Timeframe: Screening to Day 1 Predose

Population: Participants whose GFS was measured using microarrays to determine the pretreatment baseline variability in participants with blast phase Ph+ CML or Ph+ ALL.

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 \[Screening to Day 1 Predose\]).

Outcome measures

Outcome measures
Measure	Ph+ CML or Ph+ ALL n=8 Participants Participants with blast phase Ph+ CML or Ph+ ALL who were beginning treatment with imatinib, dasatinib or nilotinib as per standard of care. All participants who had evaluable gene expression data were included in the analysis.
Growth Factor Signature (GFS) Variability at Baseline	1.11 GFS Fold Ratio-Screening to Day1 Predose 90% Confidence Interval 0.90 • Interval 1.03 to 1.21

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Ph+ CML or Ph+ ALL n=9 Participants Participants with blast phase Ph+ CML or Ph+ ALL who were beginning treatment with imatinib, dasatinib or nilotinib as per standard of care. All participants who had evaluable gene expression data were included in the analysis.
Growth Factor Signature (GFS) Change From Baseline Measured by Time Weighted Average (TWA) for Days 1 to 22	0.74 GFS Fold Ratio-TWA[Days1-22] to baseline Interval 0.66 to 0.83

Adverse Events

Ph+ CML or Ph+ ALL

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place