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

Primary Purpose

Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML), Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL)

Status
Terminated
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Comparator: Biomarker evaluation
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

    • For Part II:
  • 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:

  • Participant is currently participating in or has participated in a study with an investigational compound or device within 30 days or 5 half-lives, whichever is longer, of the start of treatment
  • Participant has known human immunodeficiency virus (HIV) infection or HIV-related malignancy
  • Participant is a female who is pregnant or breastfeeding, or is expecting to conceive within the projected duration of the study
  • Participant has a known allergy or hypersensitivity to imatinib, dasatinib or nilotinib
  • Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate
  • Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • There is any concern by the investigator regarding the safe participation of the participant in the study or for any other reason, the investigator considers the participant inappropriate for participation in the study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Ph+ CML or Ph+ ALL

    Arm Description

    GFS biomarker evaluation

    Outcomes

    Primary Outcome Measures

    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]).
    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.

    Secondary Outcome Measures

    Full Information

    First Posted
    March 5, 2009
    Last Updated
    September 28, 2015
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00860535
    Brief Title
    Growth Factor Signature (GFS) Pilot Study (MK0000-098)(COMPLETED)
    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 Chromosome Positive Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphocytic Leukemia
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2015
    Overall Recruitment Status
    Terminated
    Study Start Date
    June 2009 (undefined)
    Primary Completion Date
    April 2010 (Actual)
    Study Completion Date
    June 2010 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML), Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL)

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    9 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Ph+ CML or Ph+ ALL
    Arm Type
    Experimental
    Arm Description
    GFS biomarker evaluation
    Intervention Type
    Other
    Intervention Name(s)
    Comparator: Biomarker evaluation
    Intervention Description
    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.
    Primary Outcome Measure Information:
    Title
    Growth Factor Signature (GFS) Variability at Baseline
    Description
    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
    Title
    Growth Factor Signature (GFS) Change From Baseline Measured by Time Weighted Average (TWA) for Days 1 to 22
    Description
    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

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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 For Part II: 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: Participant is currently participating in or has participated in a study with an investigational compound or device within 30 days or 5 half-lives, whichever is longer, of the start of treatment Participant has known human immunodeficiency virus (HIV) infection or HIV-related malignancy Participant is a female who is pregnant or breastfeeding, or is expecting to conceive within the projected duration of the study Participant has a known allergy or hypersensitivity to imatinib, dasatinib or nilotinib Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate Participant has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial There is any concern by the investigator regarding the safe participation of the participant in the study or for any other reason, the investigator considers the participant inappropriate for participation in the study
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Monitor
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

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

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