Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML)Phase 1NCT00860535
Growth Factor Signature (GFS) Pilot Study (MK0000-098)(COMPLETED)
A Phase 1 study testing Comparator: Biomarker evaluation in people with Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL), run by Merck Sharp & Dohme LLC.
Trial summary
This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML), Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL)
- What is being tested?
- Comparator: Biomarker evaluation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- Jun 2009to Jun 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
About this study
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
This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors.
- Conditions
- Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML), Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL)
- Being tested
- Comparator: Biomarker evaluation
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comparator: Biomarker evaluationOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Ph+ CML or Ph+ ALL | Experimental | GFS biomarker evaluation Receives: Other: Comparator: Biomarker evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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]).
Measured: 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.
Measured: Baseline to 22 Days After Initiation of Therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2009 (estimated)
- Study startJun 2009
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML)Studies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00860535
- Sponsor's protocol ID
- 0000-098
- Other IDs
- 2009_558
- Status last verified
- Sep 2015
- First submitted
- 5 Mar 2009
- Last updated
- 30 Sep 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00860535
- Acronym / sponsor ID
- 0000-098
- Conditions
- Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML), Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 12 Mar 2009 (estimated)
- Results
- Posted 10 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate a gene expression signature (Growth Factor Signature [GFS]) as a biomarker for response/resistance to BRC-ABL oncogene inhibitors.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ph+ CML or Ph+ ALL | Experimental | Other: Comparator: Biomarker evaluationGFS biomarker evaluation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Comparator: Biomarker evaluationPatients 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. | Other | Ph+ CML or Ph+ ALL |
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Comparator: Biomarker evaluation in people with Blast Phase Philadelphia Chromosomes Positive (Ph+) Chronic Myelogenous Leukemia (CML) and Philadelphia Chromosome Positive (Ph+) Acute Lymphocytic Leukemia (ALL), run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Growth Factor Signature (GFS) Variability at Baseline (time frame: Screening to Day 1 Predose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2015.