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A Study of Dasatinib in Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00482703
Collaborator
(none)
23
Enrollment
9
Locations
2
Arms
24
Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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)

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
23 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
May 1, 2007
Actual Primary Completion Date :
May 1, 2009
Actual Study Completion Date :
May 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: A

Drug: Dasatinib
tablets, Oral, 100 mg, once daily
Other Names:
  • Sprycel
  • BMS-354825

    		•
    Experimental: B

    Drug: dasatinib
    tablets, Oral, 50 mg, twice daily
    Other Names:
  • Sprycel
  • BMS-354825

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24 [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).

    Secondary Outcome Measures

    1. Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment [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.]

      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.

    2. Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24 [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.

    3. Time to Major Cytogenetic Response (MCyR) [time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met]

      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

    4. Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics [Six or more peripheral blood samples were collected at any visit after Day 7, pre-dose and 5 - 8 hours after dose administration.]

      Blood sample collection for pharmacokinetic (PK) analysis that will contribute to PK modeling.

    5. Duration of MCyR [from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death]

      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

    6. Time to CHR [time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met]

      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.

    7. Duration of CHR [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]

      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.

    8. Progression-Free Survival (PFS) [time from first dose of Dasatinib (BMS-354825) until the first day criteria for CCyR or PCyR, whichever occurs first, are first met]

      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.

    9. Expression of BCR-ABL Gene Mutations of RNA (mRNA) [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.)]

      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.

    10. Mutational Spectrum of BCR-ABL [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.)]

      Number of participants with a particular BCR-ABL mutation at Baseline and End-of-Study.

    11. Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study [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 (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).

    12. Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study [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.)]

      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.

    Other Outcome Measures

    1. Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table) [Months 0, 4, 8, 12, 16, 20, 24]

      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 BM: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35

    2. Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table) [Months 0, 4, 8, 12, 16, 20, 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.

    3. Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table) [Months 0, 4, 8, 12, 16, 20, 24]

      Progressed disease=achieving a CHR and subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose and an increase in white blood cell count (doubling of the count from lowest value to >20,000/mm3 or an increase by >50,000/mm3 on 2 assessments done at least 2 weeks apart); meeting the criteria of accelerated or blastic phase CML at any time; having an MCyR and subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a >=30% absolute increase in number of Ph+ metaphases.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • 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

    Exclusion Criteria:

    • 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

    • 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Local Institution Nagoya Aichi Japan 464-8681
    2 Local Institution Nishinomiya-Shi Hyogo Japan 663-8501
    3 Local Institution Kagoshima-Shi Kagoshima Japan 890-0064
    4 Local Institution Isehara-Shi Kanagawa Japan 259-1193
    5 Local Institution Hamamatsu-Shi Shizuoka Japan 431-3192
    6 Local Institution Bunkyo-Ku Tokyo Japan 113-8677
    7 Local Institution Chuo-Ku Tokyo Japan 104-0045
    8 Local Institution Shibuya-Ku Tokyo Japan 150-8935
    9 Local Institution Kyoto Japan

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00482703
    Other Study ID Numbers:
    • CA180-138
    First Posted:
    Jun 5, 2007
    Last Update Posted:
    Dec 17, 2010
    Last Verified:
    Nov 1, 2010
    Keywords provided by , ,
    Imatinib resistant or intolerant chronic phase CML
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Philadelphia Chromosome
    Dasatinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose
    Arm/Group Description Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity. Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
    Period Title: Overall Study
    STARTED 11 12
    COMPLETED 10 12
    NOT COMPLETED 1 0

    Baseline Characteristics

    Arm/Group Title Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose Total
    Arm/Group Description Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity. Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity. Total of all reporting groups
    Overall Participants 11 12 23
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.5
    (14.2)
    49.9
    (16.0)
    49.3
    (14.8)
    Age, Customized (participants) [Number]
    <65 years
    9
    81.8%
    10
    83.3%
    19
    82.6%
    >=65 years
    2
    18.2%
    2
    16.7%
    4
    17.4%
    Sex: Female, Male (Count of Participants)
    Female
    3
    27.3%
    5
    41.7%
    8
    34.8%
    Male
    8
    72.7%
    7
    58.3%
    15
    65.2%
    Region of Enrollment (participants) [Number]
    Japan
    11
    100%
    12
    100%
    23
    100%
    Eastern Cooperative Oncology Group Performace Status (ECOG-PS) (participants) [Number]
    Status=0
    11
    100%
    12
    100%
    23
    100%
    Status=1
    0
    0%
    0
    0%
    0
    0%
    Status=2
    0
    0%
    0
    0%
    0
    0%
    Status=3
    0
    0%
    0
    0%
    0
    0%
    Status=4
    0
    0%
    0
    0%
    0
    0%
    Status=5
    0
    0%
    0
    0%
    0
    0%
    Imatinib Status (participants) [Number]
    Imatinib-resistant
    7
    63.6%
    7
    58.3%
    14
    60.9%
    Imatinib-intolerant
    4
    36.4%
    5
    41.7%
    9
    39.1%

    Outcome Measures

    1. Primary Outcome
    Title Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
    Description 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).
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 100 mg QD Starting Dose - Imatinib-resistant Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant Dasatinib 50 mg BID Starting Dose Cohort Dasatinib 50 mg BID Starting Dose - Imatinib-resistant Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
    Arm/Group Description All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks. Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks. Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 7 4 12 7 5
    MCyR
    45
    409.1%
    29
    241.7%
    75
    326.1%
    92
    NaN
    86
    NaN
    100
    NaN
    CCyR
    27
    245.5%
    14
    116.7%
    50
    217.4%
    58
    NaN
    43
    NaN
    80
    NaN
    2. Secondary Outcome
    Title Adverse Events (AEs), Serious Adverse Events (SAEs), Discontinuations, and Deaths During Treatment
    Description 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.
    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.

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 12
    AEs (symptoms/signs and laboratory abnormalities)
    11
    100%
    12
    100%
    SAEs (symptoms/signs and laboratory abnormalities)
    4
    36.4%
    6
    50%
    Deaths
    0
    0%
    0
    0%
    AEs that led to discontinuation
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Complete Hematologic Response (CHR) in Imatinib-Intolerant and Imatinib-Resistant Participants at Week 24
    Description 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.
    Time Frame Week 24

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 100 mg QD Starting Dose - Imatinib-resistant Dasatinib 100 mg QD Starting Dose - Imatinib-intolerant Dasatinib 50 mg BID Starting Dose Cohort Dasatinib 50 mg BID Starting Dose - Imatinib-resistant Dasatinib 50 mg BID Starting Dose - Imatinib-intolerant
    Arm/Group Description All participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks. Imatinib-resistant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks. Imatinib-intolerant participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 7 4 12 7 5
    Number (95% Confidence Interval) [percentage of participants]
    91
    827.3%
    86
    716.7%
    100
    434.8%
    83
    NaN
    86
    NaN
    80
    NaN
    4. Secondary Outcome
    Title Time to Major Cytogenetic Response (MCyR)
    Description 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
    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

    Outcome Measure Data

    Analysis Population Description
    Treated participants - responders
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 6 11
    Median (95% Confidence Interval) [months]
    5.5
    4.2
    5. Secondary Outcome
    Title Pharmacokinetics of Dasatinib (BMS-354825) as Characterized by Population Pharmacokinetics
    Description Blood sample collection for pharmacokinetic (PK) analysis that will contribute to PK modeling.
    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.

    Outcome Measure Data

    Analysis Population Description
    Blood samples were collected for PK to be included in separate population PK analyses. No study specific PK analyses were planned for this report.
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 0 0
    6. Secondary Outcome
    Title Duration of MCyR
    Description 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
    Time Frame from the first day all criteria are met for CCyR or PCyR until the date of progressed disease (PD) or death

    Outcome Measure Data

    Analysis Population Description
    Median duration was not reached at the time of this report; see Outcome Measure 14 for corresponding life table.
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 0 0
    7. Secondary Outcome
    Title Time to CHR
    Description 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.
    Time Frame time from first dose of Dasatinib (BMS-354825) until the first day CHR criteria are met

    Outcome Measure Data

    Analysis Population Description
    Treated participants - responders
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 10 10
    Median (95% Confidence Interval) [months]
    1.0
    0.6
    8. Secondary Outcome
    Title Duration of CHR
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    Median duration of CHR was not reach at the time of this report. See corresponding life table presented in Outcome Measure 15.
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 0 0
    9. Secondary Outcome
    Title Progression-Free Survival (PFS)
    Description 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.
    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

    Outcome Measure Data

    Analysis Population Description
    Median months of progression-free survival was not reached at the time of this report. See corresponding life table in Outcome Measure 16.
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 0 0
    10. Secondary Outcome
    Title Expression of BCR-ABL Gene Mutations of RNA (mRNA)
    Description 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.
    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.)

    Outcome Measure Data

    Analysis Population Description
    Treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 12
    Positive at Baseline
    11
    100%
    11
    91.7%
    Negative at Baseline
    0
    0%
    1
    8.3%
    Positive at End-of-Study
    8
    72.7%
    3
    25%
    Negative at End-of-Study
    3
    27.3%
    9
    75%
    11. Secondary Outcome
    Title Mutational Spectrum of BCR-ABL
    Description Number of participants with a particular BCR-ABL mutation at Baseline and 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.)

    Outcome Measure Data

    Analysis Population Description
    Treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 12
    G250E mutation at Baseline
    1
    9.1%
    3
    25%
    G250E mutation at End-of-Study
    1
    9.1%
    0
    0%
    F317L mutation at Baseline
    0
    0%
    0
    0%
    F317L mutation at End-of-Study
    1
    9.1%
    0
    0%
    T315I mutation at Baseline
    0
    0%
    1
    8.3%
    T315I mutation at End-of-Study
    0
    0%
    1
    8.3%
    12. Secondary Outcome
    Title Cytogenetic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
    Description 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).
    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.)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 12
    MCyR
    55
    500%
    92
    766.7%
    CCyR
    36
    327.3%
    67
    558.3%
    13. Secondary Outcome
    Title Hematologic Response in Imatinib-Intolerant and Imatinib-Resistant Participants at End of Study
    Description 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.
    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.)

    Outcome Measure Data

    Analysis Population Description
    All treated participants
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 11 12
    Number (95% Confidence Interval) [percentage of participants]
    91
    827.3%
    83
    691.7%
    14. Other Pre-specified Outcome
    Title Number of Participants With Major Cytogenetic Response at Months 0 - 24 (Duration of MCyR Life Table)
    Description 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 BM: Complete Cytogenetic Response (CCyR) = 0; Partial Cytogenetic Response (PCyR) 1 - 35
    Time Frame Months 0, 4, 8, 12, 16, 20, 24

    Outcome Measure Data

    Analysis Population Description
    Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 6)
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 6 11
    Month 0
    6
    54.5%
    11
    91.7%
    Month 4
    6
    54.5%
    9
    75%
    Month 8
    6
    54.5%
    9
    75%
    Month 12
    4
    36.4%
    8
    66.7%
    Month 16
    3
    27.3%
    3
    25%
    Month 20
    0
    0%
    1
    8.3%
    Month 24
    0
    0%
    0
    0%
    15. Other Pre-specified Outcome
    Title Number of Participants With CHR at Months 0 - 24 (Duration of MCyR Life Table)
    Description 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.
    Time Frame Months 0, 4, 8, 12, 16, 20, 24

    Outcome Measure Data

    Analysis Population Description
    Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 7)
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 6 11
    Month 0
    10
    90.9%
    10
    83.3%
    Month 4
    9
    81.8%
    10
    83.3%
    Month 8
    9
    81.8%
    8
    66.7%
    Month 12
    9
    81.8%
    8
    66.7%
    Month 16
    8
    72.7%
    7
    58.3%
    Month 20
    4
    36.4%
    4
    33.3%
    Month 24
    0
    0%
    0
    0%
    16. Other Pre-specified Outcome
    Title Number of Participants With Progression-Free Survival (PFS) at Months 0 - 24 (PFS Life Table)
    Description Progressed disease=achieving a CHR and subsequently no longer meeting criteria consistently over a consecutive 2-week period after starting maximum dose; no CHR after receiving maximum dose and an increase in white blood cell count (doubling of the count from lowest value to >20,000/mm3 or an increase by >50,000/mm3 on 2 assessments done at least 2 weeks apart); meeting the criteria of accelerated or blastic phase CML at any time; having an MCyR and subsequently no longer meeting the criteria for MCyR after starting maximum dose; or having a >=30% absolute increase in number of Ph+ metaphases.
    Time Frame Months 0, 4, 8, 12, 16, 20, 24

    Outcome Measure Data

    Analysis Population Description
    Treated participants. Median duration was not reached at the time of this report (see Outcome Measure 7)
    Arm/Group Title Dasatinib 100 mg QD Starting Dose Cohort Dasatinib 50 mg BID Starting Dose Cohort
    Arm/Group Description All participants treated with a starting dose of Dasatinib (BMS-354825) 100 mg QD oral continuous daily dosing (CCD) for 24 weeks. All participants treated with a starting Dasatinib (BMS-354825) dose of 50 mg BID oral continuous daily dosing (CCD) for 24 weeks.
    Measure Participants 6 11
    Month 0
    11
    100%
    12
    100%
    Month 4
    11
    100%
    12
    100%
    Month 8
    9
    81.8%
    10
    83.3%
    Month 12
    9
    81.8%
    10
    83.3%
    Month 16
    9
    81.8%
    10
    83.3%
    Month 20
    7
    63.6%
    7
    58.3%
    Month 24
    0
    0%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose Total
    Arm/Group Description Starting dose of 100 mg QD oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity. Starting dose of 50 mg BID oral continuous daily dosing of Dasatinib (BMS-354825) for 24 weeks. One dose escalation allowed for nonresponding participants; dose reduction mandated according to the observed toxicity.
    All Cause Mortality
    Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/11 (36.4%) 6/12 (50%) 10/23 (43.5%)
    Gastrointestinal disorders
    Enterocolitis 1/11 (9.1%) 0/12 (0%) 0/23 (0%)
    Gastrointestinal haemorrhage 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    General disorders
    Pyrexia 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Infections and infestations
    Pneumonia 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Gastroenteritis viral 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Nasopharyngitis 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Upper respiratory tract infection 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Metabolism and nutrition disorders
    Glucose tolerance impaired 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Myelodysplastic syndrome 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Interstitial lung disease 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Upper respiratory tract inflammation 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Other (Not Including Serious) Adverse Events
    Dasatinib 100 mg Once-daily (QD) Starting Dose Dasatinib 50 mg Twice-daily (BID) Starting Dose Total
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/11 (100%) 12/12 (100%) 23/23 (100%)
    Blood and lymphatic system disorders
    Anaemia 6/11 (54.5%) 6/12 (50%) 12/23 (52.2%)
    Iron deficiency anaemia 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Cardiac disorders
    Pericardial effusion 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Cardiac failure 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Ear and labyrinth disorders
    Eustachian tube obstruction 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Eye disorders
    Eyelid oedema 3/11 (27.3%) 1/12 (8.3%) 4/23 (17.4%)
    Cataract 2/11 (18.2%) 0/12 (0%) 2/23 (8.7%)
    Conjunctivitis 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Conjunctivitis allergic 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Retinopathy 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Gastrointestinal disorders
    Diarrhoea 4/11 (36.4%) 5/12 (41.7%) 9/23 (39.1%)
    Constipation 1/11 (9.1%) 5/12 (41.7%) 6/23 (26.1%)
    Dental caries 3/11 (27.3%) 1/12 (8.3%) 4/23 (17.4%)
    Gastritis 4/11 (36.4%) 0/12 (0%) 4/23 (17.4%)
    Stomatitis 2/11 (18.2%) 2/12 (16.7%) 4/23 (17.4%)
    Nausea 2/11 (18.2%) 1/12 (8.3%) 3/23 (13%)
    Vomiting 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Abdominal distension 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Abdominal pain 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Dyspepsia 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Enterocolitis 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Gastric ulcer 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Gastritis erosive 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Gingival bleeding 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Gingivitis 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Irritable bowel syndrome 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Oedema mouth 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Stomach discomfort 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Gastric dysplasia 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    General disorders
    Pyrexia 2/11 (18.2%) 4/12 (33.3%) 6/23 (26.1%)
    Oedema peripheral 2/11 (18.2%) 2/12 (16.7%) 4/23 (17.4%)
    Malaise 2/11 (18.2%) 1/12 (8.3%) 3/23 (13%)
    Chest pain 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Face oedema 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Oedema 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Fatigue 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Feeling abnormal 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Feeling hot 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Localised oedema 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Immune system disorders
    Seasonal allergy 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Infections and infestations
    Nasopharyngitis 7/11 (63.6%) 10/12 (83.3%) 17/23 (73.9%)
    Gastroenteritis 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Pharyngitis 2/11 (18.2%) 0/12 (0%) 2/23 (8.7%)
    Urinary tract infection 2/11 (18.2%) 0/12 (0%) 2/23 (8.7%)
    Bronchitis 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Rhinitis 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Enteritis infectious 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Injury, poisoning and procedural complications
    Contusion 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Tooth fracture 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Investigations
    Platelet count decreased 8/11 (72.7%) 7/12 (58.3%) 15/23 (65.2%)
    Neutrophil count decreased 7/11 (63.6%) 7/12 (58.3%) 14/23 (60.9%)
    White blood cell count decreased 5/11 (45.5%) 7/12 (58.3%) 12/23 (52.2%)
    Alanine aminotransferase increased 3/11 (27.3%) 6/12 (50%) 9/23 (39.1%)
    Lymphocyte count decreased 5/11 (45.5%) 4/12 (33.3%) 9/23 (39.1%)
    Blood creatine phosphokinase increased 1/11 (9.1%) 5/12 (41.7%) 6/23 (26.1%)
    Blood lactate dehydrogenase increased 0/11 (0%) 5/12 (41.7%) 5/23 (21.7%)
    Blood phosphorus decreased 3/11 (27.3%) 2/12 (16.7%) 5/23 (21.7%)
    Aspartate aminotransferase increased 1/11 (9.1%) 3/12 (25%) 4/23 (17.4%)
    Blood albumin decreased 3/11 (27.3%) 1/12 (8.3%) 4/23 (17.4%)
    Blood creatinine increased 3/11 (27.3%) 1/12 (8.3%) 4/23 (17.4%)
    Red blood cell count decreased 1/11 (9.1%) 3/12 (25%) 4/23 (17.4%)
    Blood sodium decreased 2/11 (18.2%) 1/12 (8.3%) 3/23 (13%)
    Haemoglobin decreased 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Liver function test abnormal 0/11 (0%) 3/12 (25%) 3/23 (13%)
    Weight decreased 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Blood alkaline phosphatase increased 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Blood potassium decreased 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Blood urea increased 2/11 (18.2%) 0/12 (0%) 2/23 (8.7%)
    Blood uric acid increased 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Electrocardiogram QT corrected interval prolonged 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Gamma-glutamyltransferase increased 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Weight increased 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Protein urine present 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Blood calcium decreased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Blood fibrinogen increased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Blood folate decreased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Blood potassium increased 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Blood pressure decreased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    C-reactive protein increased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Haematocrit decreased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Intraocular pressure increased 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Lymphocyte count increased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Neutrophil count increased 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Protein total increased 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Vitamin B12 decreased 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Metabolism and nutrition disorders
    Hypophosphataemia 1/11 (9.1%) 2/12 (16.7%) 3/23 (13%)
    Anorexia 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Hypokalaemia 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Hyperuricaemia 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Musculoskeletal and connective tissue disorders
    Myalgia 3/11 (27.3%) 3/12 (25%) 6/23 (26.1%)
    Arthralgia 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Back pain 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Flank pain 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Muscle spasms 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Muscular weakness 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Musculoskeletal pain 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Neck pain 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Spinal osteoarthritis 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Histiocytosis haematophagic 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Nervous system disorders
    Headache 2/11 (18.2%) 3/12 (25%) 5/23 (21.7%)
    Carpal tunnel syndrome 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Dizziness 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Dizziness postural 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Dysgeusia 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Somnolence 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Psychiatric disorders
    Insomnia 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Apathy 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Renal and urinary disorders
    Pollakiuria 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Reproductive system and breast disorders
    Gynaecomastia 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 4/11 (36.4%) 6/12 (50%) 10/23 (43.5%)
    Cough 3/11 (27.3%) 4/12 (33.3%) 7/23 (30.4%)
    Upper respiratory tract inflammation 3/11 (27.3%) 2/12 (16.7%) 5/23 (21.7%)
    Dyspnoea 1/11 (9.1%) 1/12 (8.3%) 2/23 (8.7%)
    Pharyngolaryngeal pain 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Epistaxis 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Interstitial lung disease 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Pharyngolaryngeal discomfort 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Skin and subcutaneous tissue disorders
    Rash 5/11 (45.5%) 9/12 (75%) 14/23 (60.9%)
    Alopecia 0/11 (0%) 2/12 (16.7%) 2/23 (8.7%)
    Skin depigmentation 2/11 (18.2%) 0/12 (0%) 2/23 (8.7%)
    Acne 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Dermatitis contact 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Pruritus 0/11 (0%) 1/12 (8.3%) 1/23 (4.3%)
    Skin exfoliation 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Urticaria 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)
    Vascular disorders
    Hypertension 2/11 (18.2%) 1/12 (8.3%) 3/23 (13%)
    Hypotension 1/11 (9.1%) 0/12 (0%) 1/23 (4.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

    Results Point of Contact

    Name/Title BMS Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00482703
    Other Study ID Numbers:
    • CA180-138
    First Posted:
    Jun 5, 2007
    Last Update Posted:
    Dec 17, 2010
    Last Verified:
    Nov 1, 2010