Myeloid Leukemia, ChronicPhase 1/2NCT00482703
A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia
A Phase 1/2 study testing Dasatinib in people with Myeloid Leukemia, Chronic, run by Bristol-Myers Squibb at 9 sites in Japan.
Trial summary
The objective is to evaluate the cytogenetic response to Dasatinib (BMS-354825) administered for 24 weeks in subjects with Imatinib resistant or intolerant chronic phase chronic myeloid leukemia (CML) once daily (QD) or twice daily. (BID) Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Myeloid Leukemia, Chronic
- What is being tested?
- Dasatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 9 sitesJapan
- Study dates
- May 2007to May 2009
- Phase
- Phase 1/2
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Philadelphia chromosome positive or bcr-abl gene positive Chronic phase Chronic Myelogenous Leukemia (CML) subjects must have primary or acquired resistance to Imatinib mesylate or have intolerance of imatinib mesylate
- Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2
- Men and women, ages 20 to 75
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized
Who cannot join
- Subjects who are eligible and willing to undergo transplantation at pre-study
- Women who are pregnant or breastfeeding
- Uncontrolled or significant cardiovascular disease
- History of significant bleeding disorder unrelated to CML
- Adequate hepatic function
- Adequate renal function
Show all 9Show fewer
- Medication that increases bleeding risk
- Medication that changes heart rhythms
- Subjects who are compulsory detained for legal reasons or treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Japan9 sites
Local Institution
Bunkyo-Ku, Tokyo, 113-8677
Local Institution
Chuo-Ku, Tokyo, 104-0045
Local Institution
Hamamatsu, Shizuoka, 431-3192
Local Institution
Isehara-Shi, Kanagawa, 259-1193
Local Institution
Kagoshima, Kagoshima-ken, 890-0064
Local Institution
Kyoto, Kyoto
Local Institution
Nagoya, Aichi-ken, 464-8681
Local Institution
Nishinomiya-Shi, Hyōgo, 663-8501
Local Institution
Shibuya-Ku, Tokyo, 150-8935
About this study
Official title: A Randomized, Multicenter, Open-label Phase II Study of Dasatinib (BMS-354825) Administered Orally at a Dose of 50mg Twice Daily or 100mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia Who Are Resistant or Intolerant to Imatinib
The objective is to evaluate the cytogenetic response to Dasatinib (BMS-354825) administered for 24 weeks in subjects with Imatinib resistant or intolerant chronic phase chronic myeloid leukemia (CML) once daily (QD) or twice daily. (BID)
- Conditions
- Myeloid Leukemia, Chronic
- Being tested
- Dasatinib
- Keywords
- Imatinib resistant or intolerant chronic phase CML
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DasatinibDrug
Also called Sprycel, BMS-354825
tablets, Oral, 100 mg, once daily
dasatinibDrug
Also called Sprycel, BMS-354825
tablets, Oral, 50 mg, twice daily
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | Not described Receives: Drug: Dasatinib |
| B | Experimental | Not described Receives: Drug: dasatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
Cytogenetic responses (CyR) are based on the percentage of Philadelphia-positive (Ph+) metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), and Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Measured: Week 24
Secondary outcomes (12)
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Measured: Throughout study period to last observation. Dosing period=6 months; if beneficial, medication may continue in the extension period (ending in January 2009). Last observation=30 days past last dosing day or the discontinuation day.
Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils < 20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Measured: Week 24
Time to Major Cytogenetic Response (MCyR)
Time to MCyR is defined as the time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met. MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Ph+ Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
Measured: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics
Blood sample collection for pharmacokinetic (PK) analysis that will contribute to PK modeling.
Measured: Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration.
Duration of MCyR
The duration of MCyR will be measured from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death. Subjects who neither progress nor die will be censored on the date of their last cytogenetic assessment.MCyR = a complete and a partial cytogenetic response (CyR), based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow sample. Percentage of Philadelphia-positive (Ph+) Cells in Metaphase in bone marrow: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
Measured: from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death
Time to CHR
Time to CHR = time from first dose of Dasatinib until the first day CHR criteria are met (provided subjects achieved a cCHR). CHR=all of the following criteria: white blood cell count ≤ upper limit of normal; platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Measured: time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met
Duration of CHR
The duration of CHR were measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death. Subjects who neither progress nor die were censored on the date of their last hematologic assessment.
Measured: measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death
Progression-Free Survival (PFS)
Progressed disease=achieving a CHR \& subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose \& increase in white blood cell count (doubling of count from lowest value to >20,000/mm3 or an increase by >50,000/mm3 on 2 assessments done ≥2 weeks apart); meeting the criteria of accelerated or blastic phase chronic myeloid leukemia at any time; having an MCyR \& subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a >=30% absolute increase in number of Ph+ metaphases.
Measured: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Number of participants with positive (>= 2.0 log copies/mg) and negative (<2.0 log copies/mg) expression of mRNA at Baseline and at end of study.
Measured: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Mutational Spectrum of BCR-ABL
Number of participants with a particular BCR-ABL mutation at Baseline and End-of-Study.
Measured: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
Cytogenetic response (CyR) as reflected in the major cytogenetic response was determined by bone marrow (BM) aspirates and are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each BM sample. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), or Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Measured: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils < 20%; no extramedullary involvement. A confirmed CHR (cCHR) is obtained when all above criteria are maintained for at least 28 days after they are first met. All hematologic responses can begin only 14 days after the dosing start date.
Measured: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2007 (estimated)
- Study startMay 2007
- Primary completionMay 2009
- Study completionMay 2009
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 Myeloid Leukemia, 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00482703
- Sponsor's protocol ID
- CA180-138
- Status last verified
- Nov 2010
- First submitted
- 4 Jun 2007
- Last updated
- 17 Dec 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Multicenter, Open-label Phase II Study of Dasatinib (BMS-354825) Administered Orally at a Dose of 50mg Twice Daily or 100mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia Who Are Resistant or Intolerant to Imatinib
- ClinicalTrials.gov ID
- NCT00482703
- Acronym / sponsor ID
- CA180-138
- Conditions
- Myeloid Leukemia, Chronic
- Keywords
- Imatinib resistant or intolerant chronic phase CML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- May 2007
- Primary completion
- May 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 5 Jun 2007 (estimated)
- Results
- Posted 30 Nov 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective is to evaluate the cytogenetic response to Dasatinib (BMS-354825) administered for 24 weeks in subjects with Imatinib resistant or intolerant chronic phase chronic myeloid leukemia (CML) once daily (QD) or twice daily. (BID)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Dasatinib |
| B | Experimental | Drug: dasatinib |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Philadelphia chromosome positive or bcr-abl gene positive Chronic phase Chronic Myelogenous Leukemia (CML) subjects must have primary or acquired resistance to Imatinib mesylate or have intolerance of imatinib mesylate
- Performance status (general conditions) specified by the Eastern Cooperative Oncology Group: 0-2
- Men and women, ages 20 to 75
- Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 3 months after the study in such a manner that the risk of pregnancy is minimized
Key exclusion criteria (9 listed)
- Subjects who are eligible and willing to undergo transplantation at pre-study
- Women who are pregnant or breastfeeding
- Uncontrolled or significant cardiovascular disease
- History of significant bleeding disorder unrelated to CML
- Adequate hepatic function
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 |
|---|---|---|
| DasatinibAlso: Sprycel, BMS-354825tablets, Oral, 100 mg, once daily | Drug | A |
| dasatinibAlso: Sprycel, BMS-354825tablets, Oral, 50 mg, twice daily | Drug | B |
Primary outcome
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
Time frame: Week 24
Cytogenetic responses (CyR) are based on the percentage of Philadelphia-positive (Ph+) metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), and Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
12 secondary outcomes
Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
Time frame: Throughout study period to last observation. Dosing period=6 months; if beneficial, medication may continue in the extension period (ending in January 2009). Last observation=30 days past last dosing day or the discontinuation day.
Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
Time frame: Week 24
Time to Major Cytogenetic Response (MCyR)
Time frame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics
Time frame: Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration.
Duration of MCyR
Time frame: from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death
Time to CHR
Time frame: time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met
Duration of CHR
Time frame: measured from the first day all criteria were first met for CHR (provided subjects achieved a cCHR), until the date PD is first reported or until death
Progression-Free Survival (PFS)
Time frame: time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met
Expression of BCR-ABL Gene Mutations of RNA (mRNA)
Time frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Mutational Spectrum of BCR-ABL
Time frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
Time frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
Time frame: Baseline and at the end of long term extension period (The enrollment period was followed by an extension period until the launch of dasatinib in Japan, January 2009.)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2010.
- 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
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dasatinib in people with Myeloid Leukemia, Chronic, run by Bristol-Myers Squibb at 9 sites in Japan.
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 4 inclusion and 9 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: finished, as of the sponsor's last update on 17 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Japan. 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 combined 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.
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 30 Nov 2010). 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?
Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24 (time frame: Week 24). 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 17 Dec 2010.