Leukemia, Myeloid, ChronicPhase 2NCT00320190
Study of Dasatinib in Patients With Chronic Phase Chronic Myeloid Leukemia and a Suboptimal Response to Imatinib
A Phase 2 study testing Imatinib and Dasatinib in people with Leukemia, Myeloid, Chronic, run by Bristol-Myers Squibb at 27 sites in 11 countries.
Trial summary
The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Chronic
- What is being tested?
- Imatinib and Dasatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 27 sitesin 11 countries
- Study dates
- Aug 2006to Jan 2010
- Phase
- Phase 2
- 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
- Chronic phase Ph^+ chronic myeloid leukemia (CML) demonstrating only a suboptimal response, defined as a hematologic response that is less than a complete hematologic response after at least 3 months of monotherapy with imatinib, 400 mg; a cytogenic response (CgR) that is less than a partial CgR (PCgR) after at least 6 months of monotherapy with imatinib, 400 mg; a PCgR after at least 12 months of monotherapy with imatinib, 400 mg; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with imatinib, 400 mg.
- Either gender
- Age of 18 years or older
Who cannot join
- Previous diagnosis of accelerated phase or blast crisis CML
- Uncontrolled or significant cardiovascular disease
- History of significant bleeding disorder unrelated to CML
- Concurrent malignancies
- Intolerance of imatinib, 400 mg
- Prior treatment with imatinib at a dose higher than 400 mg
- Prior stem cell transplantation and/or high-dose chemotherapy for CML
Trial locations and contacts
27 sites in 11 countries.
27 sites in 11 countries
France7 sites
Local Institution
Lyon, 69437
Local Institution
Marseille, 13273
Local Institution
Montpellier, 34295
Local Institution
Paris, 75475
Local Institution
Rennes, 35033
Local Institution
Strasbourg, 67091
Local Institution
Toulouse, 31059
United Kingdom4 sites
Local Institution
Glasgow, Central, G31 2ER
Local Institution
Leeds, North Yorkshire, LS9 7FT
Local Institution
London, Greater London, SE5 9RS
Local Institution
London, Greater London, W12 ONN
Russia3 sites
Local Institution
Moscow, 125167
Local Institution
Saint Petersburg, 191024
Local Institution
Saint Petersburg, 197022
Sweden3 sites
Local Institution
Lund, 221 85
Local Institution
Örebro, 70185
Local Institution
Uppsala, 751 85
Belgium2 sites
Local Institution
Antwerp, 2060
Local Institution
Charleroi, 6000
Finland2 sites
Local Institution
Helsinki, 00029
Local Institution
Tampere, 33380
About this study
Official title: An Open-label, Randomized Study of Dasatinib vs High-dose (800-mg) Imatinib in the Treatment of Subjects With Chronic Phase Chronic Myeloid Leukemia Who Have Had a Suboptimal Response After at Least 3 Months of Therapy With 400 mg Imatinib
The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. The safety of these treatments will also be evaluated.
Read the detailed description
Participants were randomized 2:1 to dasatinib or high-dose imatinib, respectively. Randomization was stratified by a suboptimal response, defined as a hematologic response less than a complete hematologic response after at least 3 months of monotherapy with 400-mg imatinib; a cytogenic response (CgR) less than a partial CgR (PCgR) after at least 6 months of monotherapy with 400-mg; a PCgR after at least 12 months of monotherapy with 400-mg imatinib; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with 400-mg imatinib.
Participants received either dasatinib or imatinib for 12 months or until disease progression, unacceptable toxicity, consent withdrawal, or study discontinuation. After 12 months, who had a confirmed major molecular response and were still receiving dasatinib, 100 mg, or imatinib, 800 mg, were eligible to extend treatment for an additional 12 months. Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.
- Conditions
- Leukemia, Myeloid, Chronic
- Being tested
- Imatinib, Dasatinib
- Keywords
- Chronic phase CML, with a suboptimal response after treatment with imatinib
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ImatinibDrug
Imatinib tablets administered orally at a dose of 400 mg twice daily. Each 400- mg dose to be taken with a meal and a large glass of water.
DasatinibDrug
Dasatinib tablets administered orally at a dose of 100 mg once daily.
| Study group | Role | What they receive |
|---|---|---|
| Dasatinib | Active comparator | Participants with chronic phase chronic myeloid leukemia (CML) who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg. Receives: Drug: Dasatinib |
| Imatinib | Active comparator | Participants with chronic phase CML who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg. Receives: Drug: Imatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)
MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.
Measured: At 12 months from baseline
Secondary outcomes (6)
Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation
AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, persistent or significant disability/incapacity, drug dependency, or drug abuse; prolongs inpatient hospitalization; or is life-threatening, a congenital anomaly/birth defect, or an important medical event. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Measured: Months 1 to 12, continuously, and Months 12 to 24, continuously
Percentage of Participants With On-study AEs of Special Interest
GI=gastrointestinal. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Grade 1=mild; Grade 2=moderate; Grade 3=severe and undesirable; Grade 4=life-threatening or disabling; Grade 5=death. Percentages based on the number of participants with a specific grade at baseline. Participants without on-study test values for a particular laboratory analyte are not included in the reporting of that analyte.
Measured: Months 1 to 12, continuously, and Months 12 to 24, continuously
Median Time to MMolR
Time to MMolR is defined as the time from first treatment dose until measurement criteria are first met for MMolR. MMolR is defined as a reduction in transcript levels of the BCR-ABL gene of at least 3 log from baseline.
Measured: At 3, 6, 9, and 12 months from baseline
Percentage of Participants With Complete Cytogenetic Response
Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.
Measured: At 6 and 12 months from baseline
Median Time to Treatment Failure
Time to treatment failure is defined as the time in days from randomization to progressive disease documented by the investigator, to death from any cause without prior progression, or to early treatment discontinuation for any reason, whichever occurs first. Participants without disease progression or who do not die and complete the 12-month study treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.
Measured: Randomization to disease progression, death, or discontinuation (to 12 months)
Median Time to Progression-free Survival
Progression-free survival is defined as the time in days from randomization to progressive disease documented by the investigator or to death from any cause without prior progression. Participants without progressive disease or who do not die and complete the 12-month treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.
Measured: Randomization to disease progression or death (to 12 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2006 (estimated)
- Study startAug 2006
- Primary completionJan 2010
- Study completionJan 2010
Why it stopped: Terminated due to slow participant accrual
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 Leukemia, Myeloid, ChronicStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00320190
- Sponsor's protocol ID
- CA180-043
- Other IDs
- EUDRACT Number: 2005-005153-22
- Status last verified
- Jul 2011
- First submitted
- 1 May 2006
- Last updated
- 30 Oct 2013
- 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 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomized Study of Dasatinib vs High-dose (800-mg) Imatinib in the Treatment of Subjects With Chronic Phase Chronic Myeloid Leukemia Who Have Had a Suboptimal Response After at Least 3 Months of Therapy With 400 mg Imatinib
- ClinicalTrials.gov ID
- NCT00320190
- Acronym / sponsor ID
- CA180-043
- Conditions
- Leukemia, Myeloid, Chronic
- Keywords
- Chronic phase CML, with a suboptimal response after treatment with imatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated due to slow participant accrual
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Aug 2006
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 3 May 2006 (estimated)
- Results
- Posted 7 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. The safety of these treatments will also be evaluated.
Detailed description
Participants were randomized 2:1 to dasatinib or high-dose imatinib, respectively. Randomization was stratified by a suboptimal response, defined as a hematologic response less than a complete hematologic response after at least 3 months of monotherapy with 400-mg imatinib; a cytogenic response (CgR) less than a partial CgR (PCgR) after at least 6 months of monotherapy with 400-mg; a PCgR after at least 12 months of monotherapy with 400-mg imatinib; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with 400-mg imatinib.
Participants received either dasatinib or imatinib for 12 months or until disease progression, unacceptable toxicity, consent withdrawal, or study discontinuation. After 12 months, who had a confirmed major molecular response and were still receiving dasatinib, 100 mg, or imatinib, 800 mg, were eligible to extend treatment for an additional 12 months. Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dasatinib | Active comparator | Drug: DasatinibParticipants with chronic phase chronic myeloid leukemia (CML) who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg. |
| Imatinib | Active comparator | Drug: ImatinibParticipants with chronic phase CML who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Chronic phase Ph^+ chronic myeloid leukemia (CML) demonstrating only a suboptimal response, defined as a hematologic response that is less than a complete hematologic response after at least 3 months of monotherapy with imatinib, 400 mg; a cytogenic response (CgR) that is less than a partial CgR (PCgR) after at least 6 months of monotherapy with imatinib, 400 mg; a PCgR after at least 12 months of monotherapy with imatinib, 400 mg; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with imatinib, 400 mg.
- Either gender
- Age of 18 years or older
Key exclusion criteria (7 listed)
- Previous diagnosis of accelerated phase or blast crisis CML
- Uncontrolled or significant cardiovascular disease
- History of significant bleeding disorder unrelated to CML
- Concurrent malignancies
- Intolerance of imatinib, 400 mg
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 |
|---|---|---|
| ImatinibImatinib tablets administered orally at a dose of 400 mg twice daily. Each 400- mg dose to be taken with a meal and a large glass of water. | Drug | Imatinib |
| DasatinibDasatinib tablets administered orally at a dose of 100 mg once daily. | Drug | Dasatinib |
Primary outcome
Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)
Time frame: At 12 months from baseline
MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.
6 secondary outcomes
Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation
Time frame: Months 1 to 12, continuously, and Months 12 to 24, continuously
Percentage of Participants With On-study AEs of Special Interest
Time frame: Months 1 to 12, continuously, and Months 12 to 24, continuously
Median Time to MMolR
Time frame: At 3, 6, 9, and 12 months from baseline
Percentage of Participants With Complete Cytogenetic Response
Time frame: At 6 and 12 months from baseline
Median Time to Treatment Failure
Time frame: Randomization to disease progression, death, or discontinuation (to 12 months)
Median Time to Progression-free Survival
Time frame: Randomization to disease progression or death (to 12 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2013.
- 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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
27 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib and Dasatinib in people with Leukemia, Myeloid, Chronic, run by Bristol-Myers Squibb at 27 sites in 11 countries.
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 3 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 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in France, United Kingdom, Russia, Sweden, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Jul 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?
Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR) (time frame: At 12 months from baseline). 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 Oct 2013.