A Phase 1 interventional study of Comparator: Biomarker evaluation in Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL), sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-09-30.
Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Diagnostic
This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 9 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
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Participant has at least 30 percent blasts in peripheral blood; or at least 30 percent lymphoblasts in peripheral blood or bone marrow
Exclusion Criteria:
GFS biomarker evaluation
Other: Comparator: Biomarker evaluation
Patients on standard of care treatment will have blood drawn to evaluate biomarker changes in response to treatment with BCR-ABL inhibitors over a \~3.5 month period. Part I will enroll patients who are beginning treatment with imatinib (recommended dose 400 mg every day \[qd\]), dasatinib (recommended dose 70 mg twice a day \[bid\]), or nilotinib (recommended dose 400 mg bid). Part II will enroll patients who are changing from imatinib therapy to either dasatinib or nilotinib. A decision to initiate Part II will be made based on analysis of the results of Part I.
Growth Factor Signature (GFS) Variability at Baseline
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 \[Screening to Day 1 Predose\]).
Time frame: Screening to Day 1 Predose
Growth Factor Signature (GFS) Change From Baseline Measured by Time Weighted Average (TWA) for Days 1 to 22
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.
Time frame: Baseline to 22 Days After Initiation of Therapy
| Milestone | Ph+ CML or Ph+ ALL |
|---|---|
| Started | 9 |
| Discontinued | 1 |
| Completed | 8 |
| Not completed | 1 |
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 \[Screening to Day 1 Predose\]).
| GFS Fold Ratio-Screening to Day1 Predose | Ph+ CML or Ph+ ALL |
|---|---|
| Growth Factor Signature (GFS) Variability at Baseline | 1.11 ± 0.90 |
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.
| GFS Fold Ratio-TWA[Days1-22] to baseline | Ph+ CML or Ph+ ALL |
|---|---|
| Growth Factor Signature (GFS) Change From Baseline Measured by Time Weighted Average (TWA) for Days 1 to 22 | 0.74 (0.66 to 0.83) |
Collected over All participants in the study were followed for all clinical adverse experiences from baseline until 5 days following any protocol specific procedure.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ph+ CML or Ph+ ALL | — | 0/9 (0%) | 0/9 (0%) |
| Age, Continuous(years) | Ph+ CML or Ph+ ALL |
|---|---|
| Mean | 48.0 ± 15.3 |
| Sex: Female, Male(Participants) | Ph+ CML or Ph+ ALL |
|---|---|
| Female | 3 |
| Male | 6 |
No study locations are listed for this record.
This study is terminated, as verified in Sep 2015. You cannot join it, but the record below documents what was studied.
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Merck Sharp & Dohme LLC