Clincosm LogoSign in Get a demo

START rollover: Long-term Safety of Dasatinib in Patients With Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00982488
Collaborator
(none)
238
Enrollment
72
Locations
5
Arms
86
Duration (Months)
3.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study assesses the long-term safety and tolerability of dasatinib administered to patients with chronic myelogenous leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia and experienced clinical benefit from treatment with dasatinib or imatinib in previous protocols.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
238 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Dasatinib in Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Subjects Who Are Experiencing Clinical Benefit on Current START or CA180-039 Protocols: Long Term Safety and Efficacy Analysis
Study Start Date :
Oct 1, 2007
Actual Primary Completion Date :
Dec 1, 2014
Actual Study Completion Date :
Dec 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Other: Dasatinib, 50 mg QD to 120 mg BID, Chronic phase

Participants with chronic phase disease continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID).

Drug: Dasatinib
Dasatinib was supplied as 20- and 50-mg tablets.
Other Names:
  • BMS-354825
  • Sprycel
  • Src Kinase

    		•
    Other: Imatinib, 400 mg BID, Chronic phase

    Participants with chronic phase disease received 400 mg of imatinib twice BID.

    Drug: Imatinib
    Imatinib was supplied as 100- and 400-mg tablets.
    Other Names:
  • Gleevec/Glivec

    		•
    Other: Dasatinib, 50 mg QD to 120 mg BID, Advanced phase, AP

    Participants with advanced phase disease, accelerated phase (AP), continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID.

    Drug: Dasatinib
    Dasatinib was supplied as 20- and 50-mg tablets.
    Other Names:
  • BMS-354825
  • Sprycel
  • Src Kinase

    		•
    Other: Dasatinib, 50 mg QD to 120 mg BID, Advanced phase, MBP

    Participants with advanced phase disease, myeloid blast cell (MBP), continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID.

    Drug: Dasatinib
    Dasatinib was supplied as 20- and 50-mg tablets.
    Other Names:
  • BMS-354825
  • Sprycel
  • Src Kinase

    		•
    Other: Dasatinib, 50 mg QD to 120 mg BID, Advanced phase, Ph+ ALL

    Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID.

    Drug: Dasatinib
    Dasatinib was supplied as 20- and 50-mg tablets.
    Other Names:
  • BMS-354825
  • Sprycel
  • Src Kinase

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest [Day 1 of treatment through a maximum of 82 months + 30 days]

      AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=drug-related; having certain, probable, possible, or unknown relationship to study drug.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    Key Inclusion Criteria

    • Signed written informed consent

    • Received treatment in protocols CA180-005, CA180-006, CA180-013, CA180-015 or CA180-017, or CA180-039

    • Received clinical benefit with dasatinib or imatinib (study CA180017) in the opinion of the Investigator

    • Men and women, ages 18 and older

    Key Exclusion Criteria

    • A serious uncontrolled medical disorder or active infection that would impair the ability of the patient to receive protocol therapy

    • Dementia or altered mental status that would prohibit the understanding or rendering of informed consent

    • Patients currently taking drugs, including but not limited to quinidine, procainamide, disopyramide, amiodarone, sotalol, ibutilide, dofetilide, erythromycins, clarithromycin, chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, ziprasidone, cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, and lidoflazine, which are generally accepted to have a risk of causing Torsades de Pointes

    • Patients taking medications known to be potent CYP3A4 inhibitors (ketoconazole, ritonavir) or inducers (rifampin, efavirenz)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pacific Cancer Medical Center Inc Anaheim California United States 92801
    2 Loma Linda University Cancer Center Loma Linda California United States 92354
    3 Ucla Department Of Medicine Los Angeles California United States 90095
    4 Stanford University School Of Medicine Stanford California United States 94305
    5 Kaiser Permanente Medical Center Vallejo California United States 94589
    6 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612
    7 University Of Chicago Chicago Illinois United States 60637
    8 Central Indiana Cancer Centers Indianapolis Indiana United States 46219
    9 University Of Kansas Medical Center Westwood Kansas United States 66205
    10 Dana Faber Cancer Institute Boston Massachusetts United States 02215
    11 University Of Michigan Medical Center Ann Arbor Michigan United States 48109
    12 Wayne State University Detroit Michigan United States 48201
    13 John Theurer Cancer Center Hackensack New Jersey United States 07601
    14 Oregon Health & Sci Univ Portland Oregon United States 97239
    15 Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224
    16 Ut Southwestern Medical Center At Dallas Dallas Texas United States 75390
    17 The University Of Texas Md Anderson Cancer Center Houston Texas United States 77030
    18 Local Institution Capital Federal Buenos Aires Argentina 1425
    19 Local Institution Buenos Aires Argentina 1021
    20 Local Institution Buenos Aires Argentina 1280
    21 Local Institution Adelaide South Australia Australia 5000
    22 Local Institution Mont-godinne Belgium 5530
    23 Local Institution Curitiba Parana Brazil 80060
    24 Local Institution Campinas San Paulo Brazil 13083
    25 Local Institution Rio de Janeiro Brazil 20231
    26 Local Institution Sao Paulo Brazil 05403
    27 Local Institution Sao Paulo Brazil 05652
    28 Local Institution Toronto Ontario Canada M4X 1K9
    29 Local Institution Montreal Quebec Canada H3A 1A1
    30 Local Institution Helsinki Finland 00029
    31 Local Institution Lille France 59000
    32 Local Institution Lyon Cedex 03 France 69437
    33 Local Institution Nantes France 44035
    34 Local Institution Paris France 75475
    35 Local Institution Pessac France 33604
    36 Local Institution Poitiers Cedex France 86021
    37 Local Institution Strasbourg France 67091
    38 Local Institution Hamburg Germany 20246
    39 Local Institution Leipzig Germany 04103
    40 Local Institution Mannheim Germany 68167
    41 Local Institution Budapest Hungary 1097
    42 Local Institution Dublin 8 Dublin Ireland
    43 Local Institution Ramat-gan Israel 52621
    44 Local Institution Bologna Italy 40138
    45 Local Institution Napoli Italy 80131
    46 Local Institution Orbassano (to) Italy 10043
    47 Local Institution Roma Italy 00144
    48 Local Institution Jeollanam-do Korea, Republic of 519-809
    49 Local Institution Seoul Korea, Republic of 137-040
    50 Local Institution Trondheim Norway 7006
    51 Local Institution Lima Peru 34
    52 Local Institution Lima Peru LIMA II
    53 Local Institution Katowice Poland 40032
    54 Local Institution Krakow Poland 31501
    55 Local Institution Lodz Poland 93-510
    56 Local Institution Lublin Poland 20081
    57 Local Institution Warsaw Poland 02097
    58 Local Institution Moscow Russian Federation 125167
    59 Local Institution St.petersburg Russian Federation 179089
    60 Local Institution Groenkloof Gauteng South Africa 0181
    61 Local Institution Parktown Gauteng South Africa 2193
    62 Local Institution Barcelona Spain 08036
    63 Local Institution Gothenburg Sweden 41345
    64 Local Institution Lund Sweden 221 85
    65 Local Institution Stockholm Sweden SE-17176
    66 Local Institution Umea Sweden 901 85
    67 Local Institution Uppsala Sweden 751 85
    68 Local Institution Basel Switzerland 4031
    69 Local Institution Bangkok Thailand 10400
    70 Local Institution London Greater London United Kingdom W12 OHS
    71 Local Institution Glasgow Scotland United Kingdom G12 OXB
    72 Local Institution Newcastle Tyne And Wear United Kingdom NE2 4HH

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00982488
    Other Study ID Numbers:
    • CA180-188
    • 2007-003624-37
    First Posted:
    Sep 23, 2009
    Last Update Posted:
    Jan 22, 2016
    Last Verified:
    Dec 1, 2015
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Philadelphia Chromosome
    Imatinib Mesylate
    Dasatinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail A total of 238 patients were enrolled: 200 with chronic phase chronic myelogenous leukemia (CML) and 38 with advanced phase disease (34 with acclelerated phase CML, 3 with myeloid blast phase CML, and 1 with Philadelphia chromosome positive acute lymphoblastic leukemia.) All but 1 CML patient, who no longer met study criteria, received treatment.
    Arm/Group Title Dasatinib 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MPB Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL
    Arm/Group Description Participants with chronic phase disease were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID). Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants chronic phase disease received 400 mg of imatinib BID. Dose reduction to 600 mg/day (300 mg BID) was permitted, provided the participant had not previously received that dose prior to entry into CA180-017. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, accelerated phase (AP) were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, myeloid blast phase (MPB), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure.
    Period Title: Overall Study
    STARTED 185 14 34 3 1
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 185 14 34 3 1

    Baseline Characteristics

    Arm/Group Title Dasatinib 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MPB Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL Total
    Arm/Group Description Participants with chronic phase disease were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID). Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with chronic phase disease received 400 mg of imatinib BID. Dose reduction to 600 mg/day (300 mg BID) was permitted, provided the participant had not previously received that dose prior to entry into CA180-017. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, accelerated phase (AP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, myeloid blast phase (MPB), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Total of all reporting groups
    Overall Participants 185 14 34 3 1 237
    Age, Customized (Number) [Number]
    Younger than 21 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    21-45 years
    46
    24.9%
    5
    35.7%
    7
    20.6%
    0
    0%
    0
    0%
    58
    24.5%
    46-65 years
    88
    47.6%
    5
    35.7%
    17
    50%
    3
    100%
    1
    100%
    114
    48.1%
    66-75 years
    40
    21.6%
    3
    21.4%
    9
    26.5%
    0
    0%
    0
    0%
    52
    21.9%
    Older than 75 years
    11
    5.9%
    1
    7.1%
    1
    2.9%
    0
    0%
    0
    0%
    13
    5.5%
    Sex: Female, Male (Count of Participants)
    Female
    91
    49.2%
    6
    42.9%
    15
    44.1%
    2
    66.7%
    1
    100%
    115
    48.5%
    Male
    94
    50.8%
    8
    57.1%
    19
    55.9%
    1
    33.3%
    0
    0%
    122
    51.5%
    Race/Ethnicity, Customized (Number) [Number]
    White
    167
    90.3%
    10
    71.4%
    26
    76.5%
    2
    66.7%
    1
    100%
    206
    86.9%
    Black/African American
    8
    4.3%
    0
    0%
    2
    5.9%
    0
    0%
    0
    0%
    10
    4.2%
    Asian
    7
    3.8%
    1
    7.1%
    6
    17.6%
    0
    0%
    0
    0%
    14
    5.9%
    Other
    3
    1.6%
    3
    21.4%
    0
    0%
    1
    33.3%
    0
    0%
    7
    3%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Died and Had Serious Adverse Events (SAEs), Related SAEs, Adverse Events (AEs) Leading to Discontinuation, Related AEs Leading to Discontinuation, Related AEs, and Related AEs of Special Interest
    Description AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=drug-related; having certain, probable, possible, or unknown relationship to study drug.
    Time Frame Day 1 of treatment through a maximum of 82 months + 30 days

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug
    Arm/Group Title Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, Ph+ ALL
    Arm/Group Description Participants with chronic phase disease were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID). Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with chronic phase disease received 400 mg of imatinib twice daily (BID). Dose reduction to 600 mg/day (300 mg BID) was permitted, provided the participant had not previously received that dose prior to entry into CA180-017. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, accelerated phase (AP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, myeloid blast phase (MBP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID . Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure.
    Measure Participants 185 14 34 3 1
    All deaths
    22
    11.9%
    0
    0%
    4
    11.8%
    0
    0%
    0
    0%
    Deaths within 30 days of last dose
    9
    4.9%
    0
    0%
    2
    5.9%
    0
    0%
    0
    0%
    SAEs
    57
    30.8%
    3
    21.4%
    15
    44.1%
    1
    33.3%
    1
    100%
    Drug-related SAEs
    28
    15.1%
    2
    14.3%
    9
    26.5%
    0
    0%
    0
    0%
    AEs leading to discontinuation
    39
    21.1%
    1
    7.1%
    10
    29.4%
    0
    0%
    1
    100%
    Drug-related AEs leading to discontinuation
    29
    15.7%
    1
    7.1%
    8
    23.5%
    0
    0%
    0
    0%
    Drug-related AEs
    140
    75.7%
    7
    50%
    27
    79.4%
    2
    66.7%
    0
    0%
    Drug-related AEs of special interest
    111
    60%
    4
    28.6%
    20
    58.8%
    1
    33.3%
    0
    0%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP Dasatinib, 50 mg QD to 120 mg, Advanced Phase, Ph+ ALL
    Arm/Group Description Participants with chronic phase disease were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg once daily (QD) to 120 mg twice daily (BID). Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with chronic phase disease received 400 mg of imatinib BID. Dose reduction to 600 mg/day (300 mg BID) was permitted, provided the participant had not previously received that dose prior to entry into CA180-017. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, accelerated phase (AP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID. Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, myeloid blast phase (MBP), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID. Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure. Participants with advanced phase disease, Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), were rolled over from previous studies CA180-039, CA180-043, and the SRC/ABL tyrosine kinase inhibition activity: Research trials (START). Participants continued on the previous study dose of dasatinib, ranging from 50 mg QD to 120 mg BID. Dose escalations to optimize response and dose reductions for toxicity were permitted. Participants received study medication until disease progression, unacceptable toxicity, failure to serve patient's best interest, withdrawal of consent, or study closure.
    All Cause Mortality
    Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP Dasatinib, 50 mg QD to 120 mg, Advanced Phase, Ph+ ALL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP Dasatinib, 50 mg QD to 120 mg, Advanced Phase, Ph+ ALL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 57/185 (30.8%) 3/14 (21.4%) 15/34 (44.1%) 1/3 (33.3%) 1/1 (100%)
    Cardiac disorders
    Atrial fibrillation 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Bradyarrhythmia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Supraventricular tachycardia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Cardiac failure congestive 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Cardiac failure 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Myocardial infarction 1/185 (0.5%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Acute myocardial infarction 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Left ventricular dysfunction 1/185 (0.5%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Pericardial effusion 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Eye disorders
    Retinal artery occlusion 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Vision blurred 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 2/185 (1.1%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Large intestinal haemorrhage 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Pancreatitis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Intestinal obstruction 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Abdominal distension 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Ascites 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Diarrhoea 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Small intestinal obstruction 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Volvulus 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Lower gastrointestinal haemorrhage 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Pancreatitis acute 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Abdominal pain 1/185 (0.5%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Large intestine polyp 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    General disorders
    Disease progression 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Oedema peripheral 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Chest pain 1/185 (0.5%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Effusion 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Death 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Pain 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Pyrexia 5/185 (2.7%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Sudden death 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Hepatobiliary disorders
    Cholelithiasis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Cholecystitis 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Infections and infestations
    Appendicitis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Cellulitis 2/185 (1.1%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Infection 3/185 (1.6%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Erysipelas 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Localised infection 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Pneumonia 5/185 (2.7%) 0/14 (0%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Pseudomembranous colitis 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Sepsis 3/185 (1.6%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Staphylococcal infection 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Injury, poisoning and procedural complications
    Procedural haemorrhage 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Lower limb fracture 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Subdural haematoma 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Transfusion reaction 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Post procedural haemorrhage 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Splenic rupture 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Hyponatraemia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Obesity 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Musculoskeletal and connective tissue disorders
    Bone pain 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Intervertebral disc protrusion 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Osteoarthritis 0/185 (0%) 0/14 (0%) 0/34 (0%) 1/3 (33.3%) 0/1 (0%)
    Spinal pain 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Arthralgia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Groin pain 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Back pain 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute lymphocytic leukaemia recurrent 0/185 (0%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 1/1 (100%)
    Bladder cancer 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Bladder cancer recurrent 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Malignant neoplasm progression 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Tumour flare 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Breast cancer 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Chronic myeloid leukaemia 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Neoplasm 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Uterine leiomyoma 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Nervous system disorders
    Peripheral sensory neuropathy 1/185 (0.5%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Transient ischaemic attack 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    VIIth nerve paralysis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Cerebrovascular accident 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Psychiatric disorders
    Depression 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Renal and urinary disorders
    Proteinuria 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Renal failure acute 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Renal impairment 0/185 (0%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 1/1 (100%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary arterial hypertension 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Pulmonary embolism 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Haemothorax 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Pleural effusion 13/185 (7%) 1/14 (7.1%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Dyspnoea 3/185 (1.6%) 0/14 (0%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Pulmonary hypertension 2/185 (1.1%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Nasal septum perforation 0/185 (0%) 0/14 (0%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Lung infiltration 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Social circumstances
    Elderly 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Surgical and medical procedures
    Oophorectomy bilateral 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Vascular disorders
    Deep vein thrombosis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Hypotension 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Thrombosis 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Peripheral ischaemia 1/185 (0.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Dasatinib, 50 mg QD to 120 mg BID, Chronic Phase Imatinib, 400 mg BID, Chronic Phase Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, AP Dasatinib, 50 mg QD to 120 mg BID, Advanced Phase, MBP Dasatinib, 50 mg QD to 120 mg, Advanced Phase, Ph+ ALL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 138/185 (74.6%) 10/14 (71.4%) 24/34 (70.6%) 2/3 (66.7%) 0/1 (0%)
    Blood and lymphatic system disorders
    Thrombocytopenia 8/185 (4.3%) 1/14 (7.1%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Neutropenia 8/185 (4.3%) 1/14 (7.1%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Cardiac disorders
    Diastolic dysfunction 0/185 (0%) 0/14 (0%) 0/34 (0%) 1/3 (33.3%) 0/1 (0%)
    Nodal arrhythmia 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Gastrointestinal disorders
    Dyspepsia 2/185 (1.1%) 1/14 (7.1%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Constipation 9/185 (4.9%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Abdominal distension 3/185 (1.6%) 1/14 (7.1%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Diarrhoea 19/185 (10.3%) 2/14 (14.3%) 2/34 (5.9%) 1/3 (33.3%) 0/1 (0%)
    Nausea 8/185 (4.3%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Vomiting 4/185 (2.2%) 3/14 (21.4%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    General disorders
    Oedema peripheral 25/185 (13.5%) 1/14 (7.1%) 4/34 (11.8%) 0/3 (0%) 0/1 (0%)
    Face oedema 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Fatigue 25/185 (13.5%) 1/14 (7.1%) 3/34 (8.8%) 1/3 (33.3%) 0/1 (0%)
    Pyrexia 15/185 (8.1%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Infections and infestations
    Viral infection 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Gastroenteritis 2/185 (1.1%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Upper respiratory tract infection 10/185 (5.4%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Fungal skin infection 1/185 (0.5%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Gastrointestinal infection 1/185 (0.5%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Localised infection 0/185 (0%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Nasopharyngitis 7/185 (3.8%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Peritonsillar abscess 0/185 (0%) 0/14 (0%) 0/34 (0%) 1/3 (33.3%) 0/1 (0%)
    Sinusitis 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Investigations
    Aspartate aminotransferase increased 1/185 (0.5%) 0/14 (0%) 1/34 (2.9%) 1/3 (33.3%) 0/1 (0%)
    Activated partial thromboplastin time prolonged 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Alanine aminotransferase increased 2/185 (1.1%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Blood fibrinogen decreased 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Blood bilirubin 0/185 (0%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Lipase increased 0/185 (0%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 12/185 (6.5%) 0/14 (0%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Osteoarthritis 3/185 (1.6%) 0/14 (0%) 0/34 (0%) 1/3 (33.3%) 0/1 (0%)
    Myalgia 8/185 (4.3%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Osteoporosis 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Arthralgia 14/185 (7.6%) 0/14 (0%) 1/34 (2.9%) 1/3 (33.3%) 0/1 (0%)
    Back pain 11/185 (5.9%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Nervous system disorders
    Dizziness 13/185 (7%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Neuropathy peripheral 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Headache 14/185 (7.6%) 1/14 (7.1%) 1/34 (2.9%) 0/3 (0%) 0/1 (0%)
    Psychiatric disorders
    Insomnia 6/185 (3.2%) 1/14 (7.1%) 1/34 (2.9%) 1/3 (33.3%) 0/1 (0%)
    Renal and urinary disorders
    Proteinuria 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Renal failure 1/185 (0.5%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Haematuria 0/185 (0%) 0/14 (0%) 2/34 (5.9%) 0/3 (0%) 0/1 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion 67/185 (36.2%) 1/14 (7.1%) 17/34 (50%) 1/3 (33.3%) 0/1 (0%)
    Dyspnoea 33/185 (17.8%) 0/14 (0%) 5/34 (14.7%) 0/3 (0%) 0/1 (0%)
    Cough 20/185 (10.8%) 0/14 (0%) 4/34 (11.8%) 0/3 (0%) 0/1 (0%)
    Dyspnoea exertional 8/185 (4.3%) 0/14 (0%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin 2/185 (1.1%) 1/14 (7.1%) 0/34 (0%) 0/3 (0%) 0/1 (0%)
    Rash 31/185 (16.8%) 0/14 (0%) 4/34 (11.8%) 0/3 (0%) 0/1 (0%)
    Pruritus 5/185 (2.7%) 0/14 (0%) 2/34 (5.9%) 1/3 (33.3%) 0/1 (0%)
    Vascular disorders
    Hypertension 12/185 (6.5%) 0/14 (0%) 3/34 (8.8%) 0/3 (0%) 0/1 (0%)

    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 Bristol-Myers Squibb Study Director
    Organization Bristol-Myers Squibb
    Phone
    Email Clinical.Trials@bms.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT00982488
    Other Study ID Numbers:
    • CA180-188
    • 2007-003624-37
    First Posted:
    Sep 23, 2009
    Last Update Posted:
    Jan 22, 2016
    Last Verified:
    Dec 1, 2015