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| ID | Type | Description | Link |
|---|---|---|---|
| 2009_558 |
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This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ph+ CML or Ph+ ALL | Experimental | GFS biomarker evaluation |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Comparator: Biomarker evaluation | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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]). | 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. | Baseline to 22 Days After Initiation of Therapy |
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Inclusion Criteria:
Participant must have a histologically or cytopathologically confirmed blast phase Ph+ CML or Ph+ ALL.
Participant is 18 years of age on the day of signing informed consent
Participant must have performance status 0-3 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Participant has at least 30 percent blasts in peripheral blood; or at least 30 percent lymphoblasts in peripheral blood or bone marrow
Participant has progressed while taking imatinib or is unable to tolerate imatinib, being defined as discontinuing imatinib treatment as a result of nonhematologic toxic effects of any grade
If female, participant is either post-menopausal, free from menses for >2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1
Female participants of childbearing potential must have a negative serum or urine pregnancy test (beta hCG) at screening
If male, participant is surgically sterilized, agrees to use an adequate method of contraception, or agrees to abstain from heterosexual activity for the duration of the study
Participant or the patrticipant's legal representative has voluntarily agreed to participate by giving written informed consent
Participant must be available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Merck Sharp & Dohme LLC | Study Director |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ph+ CML or Ph+ ALL | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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]). | Participants whose GFS was measured using microarrays to determine the pretreatment baseline variability in participants with blast phase Ph+ CML or Ph+ ALL. | Posted | Mean | 90% Confidence Interval | GFS Fold Ratio-Screening to Day1 Predose | Screening to Day 1 Predose |
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All participants in the study were followed for all clinical adverse experiences from baseline until 5 days following any protocol specific procedure.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ph+ CML or Ph+ ALL | Participants with blast phase Ph+ CML or Ph+ ALL who were beginning treatment with imatinib, dasatinib or nilotinib as per standard of care. |
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Part I aimed to have 10 evaluable patients. Due to slow enrollment, 9 patients who met the inclusion/exclusion criteria were enrolled over a period of 9 months. Part I was terminated early and Part II was cancelled due to slow enrollment.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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|
| years |
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| Sex: Female, Male | Count of Participants | 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. |
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| Primary | 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. | Posted | Mean | 90% Confidence Interval | GFS Fold Ratio-TWA[Days1-22] to baseline | Baseline to 22 Days After Initiation of Therapy |
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| 0 |
| 9 |
| 0 |
| 9 |
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| D009196 |
| Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |