Clincosm LogoSign in Get a demo

A Phase 1B Study to Investigate the Safety and Preliminary Efficacy for the Combination of Dasatinib Plus Nivolumab in Patients With Chronic Myeloid Leukemia

Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT02011945
Collaborator
(none)
35
Enrollment
21
Locations
3
Arms
58.6
Actual Duration (Months)
1.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find a dose of Nivolumab that can be safely added to Dasatinib in patients with Chronic Myeloid Leukemia.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
35 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1B Dose Escalation Study to Investigate the Safety, Tolerability and Preliminary Efficacy for the Combination Dasatinib (BMS-354825) Plus Nivolumab (BMS-936558) in Patients Chronic Myeloid Leukemia (CML)
Actual Study Start Date :
Feb 7, 2014
Actual Primary Completion Date :
Dec 26, 2018
Actual Study Completion Date :
Dec 26, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: dasatinib Only

dasatinib 100 mg QD(CP) or 140 mg QD (AP)

Drug: Dasatinib
Other Names:
  • BMS-354825

    		•
    Experimental: Dose Level 1

    Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

    Drug: Dasatinib
    Other Names:
  • BMS-354825

    • Drug: Nivolumab
    Other Names:
  • BMS-936558

    		•
    Experimental: Dose Level 2

    Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)

    Drug: Dasatinib
    Other Names:
  • BMS-354825

    • Drug: Nivolumab
    Other Names:
  • BMS-936558

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Dose Limiting Toxicities (DLT) [Week 3 to week 6]

      DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: Grade 4 hematologic AE lasting > 7 days despite appropriate medical intervention, except as noted below; Grade 3 or Grade 4 nonhematologic AE irrespective of duration; Grade 2 nonhematologic AE lasting > 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); Any toxicity managed by discontinuation of nivolumab; Grade ≥ 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for > 28 consecutive days; Grade ≥ 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.

    2. Incidence of Adverse Events (AEs) [Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days]

      Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.

    3. Incidence of Serious Adverse Events (SAEs) [Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing]

      Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.

    4. Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology [Up to 40 Months]

      The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology

    5. Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests [Up to 40 Months]

      The number of participants with an abnormal Liver function test. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)

    6. Incidence of Laboratory Abnormalities in Specific Thyroid Tests [Up to 40 Months]

      Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)

    Secondary Outcome Measures

    1. Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

    2. Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

    3. Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).

    4. Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

    5. Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

    6. Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants [upto 36 Months]

      Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).

    7. Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    8. Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    9. Time to Major Molecular Response (MMR) - CML-AP Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    10. Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants [Up to 36 Months]

      will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    11. Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants [Up to 36 Months]

      will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    12. Duration of Major Molecular Response (MMR) - CML-AP Participants [Up to 36 Months]

      will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    13. Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    14. Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    15. Time to Molecular Response 4.5(MR4.5) - CML-AP Participants [Up to 36 Months]

      measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.

    16. Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants [Up to 36 Months]

      will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    17. Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants [Up to 36 Months]

      will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    18. Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants [Up to 36 Months]

      will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment

    Eligibility Criteria

    Criteria

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

    For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

    Inclusion Criteria:

    • Confirmed diagnosis of Chronic Myeloid Leukemia in Chronic Phase or Accelerated Phase :

    • With historically documented Ph+ cells

    • ≥2 prior Tyrosine Kinase Inhibitors (TKI) therapies for CML

    • Currently progressing, resistance to or with a suboptimal response to their most recent therapy

    • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Score 0 - 1

    Exclusion Criteria:

    • Blast phase CML

    • Known Abl-kinase mutation resistant to Dasatinib (e.g. T315I or T315A)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Winship Cancer Institute Atlanta Georgia United States 30322
    2 Dana Farber Cancer Institute. Boston Massachusetts United States 02215
    3 Ut Southwestern Medical Center At Dallas Dallas Texas United States 75390
    4 The University Of Texas MD Anderson Cancer Center Houston Texas United States 77030
    5 Froedtert Hospital & Medical College of Wisconsin Milwaukee Wisconsin United States 53226
    6 Local Institution St Leonards New South Wales Australia 2065
    7 Local Institution Adelaide South Australia Australia 5000
    8 Local Institution Parkville Victoria Australia 3050
    9 QEII Health Sciences Centre-VG Site Halifax Nova Scotia Canada B3H 2Y9
    10 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 2M9
    11 Hopital Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4
    12 Local Institution Bordeaux France 33000
    13 Campus Virchow Klinikum Der Charite Berlin Germany 13353
    14 Universitaetsklinikum Bonn Bonn Germany 53127
    15 Universitaetsklinikum Carl Gustav Carus Dresden Germany 01307
    16 Universitaetsklinik Frankfurt Frankfurt am Main Germany 60590
    17 Local Institution Napoli Italy 80131
    18 Local Institution Orbassano Italy 10043
    19 Local Institution Roma Italy 00161
    20 Local Institution Madrid Spain 28047
    21 Local Institution Valencia Spain 46010

    Sponsors and Collaborators

    • Bristol-Myers Squibb

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02011945
    Other Study ID Numbers:
    • CA180-373
    • 2013-002156-33
    First Posted:
    Dec 16, 2013
    Last Update Posted:
    Mar 18, 2020
    Last Verified:
    Feb 1, 2020
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myelogenous, Chronic, BCR-ABL Positive
    Nivolumab
    Dasatinib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 35 Participants enrolled; 31 participants randomized. Reasons not randomized: 1 participant withdrew consent, 3 participants no longer met the study criteria.
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Period Title: Overall Study
    STARTED 2 13 16
    COMPLETED 0 3 6
    NOT COMPLETED 2 10 10

    Baseline Characteristics

    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2 Total
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Total of all reporting groups
    Overall Participants 2 13 16 31
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    48.5
    (13.4)
    61.2
    (12.4)
    47.1
    (13.6)
    53.1
    (14.5)
    Sex: Female, Male (Count of Participants)
    Female
    1
    50%
    7
    53.8%
    5
    31.3%
    13
    41.9%
    Male
    1
    50%
    6
    46.2%
    11
    68.8%
    18
    58.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    1
    6.3%
    1
    3.2%
    Not Hispanic or Latino
    0
    0%
    4
    30.8%
    8
    50%
    12
    38.7%
    Unknown or Not Reported
    2
    100%
    9
    69.2%
    7
    43.8%
    18
    58.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    6.3%
    1
    3.2%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    2
    15.4%
    2
    12.5%
    4
    12.9%
    White
    2
    100%
    11
    84.6%
    13
    81.3%
    26
    83.9%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Incidence of Dose Limiting Toxicities (DLT)
    Description DLT will be determined based on the incidence and intensity of drug related adverse events (AEs). The following drug-related AEs (whether related to one or both agents) occurring during the first 6 weeks of combined treatment with both dasatinib plus nivolumab (ie, Weeks 3 to 8, inclusive) would be considered DLTs: Grade 4 hematologic AE lasting > 7 days despite appropriate medical intervention, except as noted below; Grade 3 or Grade 4 nonhematologic AE irrespective of duration; Grade 2 nonhematologic AE lasting > 7 days despite appropriate medical intervention (exception: asymptomatic laboratory values of Grade 2 which do not require medical intervention); Any toxicity managed by discontinuation of nivolumab; Grade ≥ 2 AE not controlled by medical intervention and requiring dasatinib treatment interruption for > 28 consecutive days; Grade ≥ 2 AE not controlled by medical intervention and requiring missing 2 consecutive doses of nivolumab.
    Time Frame Week 3 to week 6

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    Number [Number of Incidence]
    0
    0
    0
    2. Primary Outcome
    Title Incidence of Adverse Events (AEs)
    Description Any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product, whether or not considered related to the investigational product.
    Time Frame Initiation of study drug to discontinuation of nivolumab stop date + 100 days or discontinuation of dasatinib + 30 days

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    CML-CP, No Prior dasatinib treatment
    1
    2
    CML-CP, Prior dasatinib treatment
    1
    8
    11
    CML-AP participants
    4
    3
    3. Primary Outcome
    Title Incidence of Serious Adverse Events (SAEs)
    Description Any untoward medical occurrence that at any dose: results in death, is life threatening, requires in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is a important medical event.Requires inpatient hospitalization or causes prolongation of existing hospitalization, results.
    Time Frame Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    CML-CP, No Prior dasatinib treatment
    0
    2
    CML-CP, Prior dasatinib treatment
    0
    3
    4
    CML-AP participants
    4
    2
    4. Primary Outcome
    Title Incidence of Change From Baseline in Clinical Laboratory Tests: Hematology
    Description The number of participants with a shift in laboratory test results from baseline to Grade 3-4 in hematology
    Time Frame Up to 40 Months

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    Hemoglobin
    0
    0%
    2
    15.4%
    4
    25%
    Platelets
    0
    0%
    5
    38.5%
    4
    25%
    Absolute Neutrophil Count (ANC)
    0
    0%
    5
    38.5%
    3
    18.8%
    White Blood Cell (WBC)
    0
    0%
    1
    7.7%
    3
    18.8%
    5. Primary Outcome
    Title Incidence of Abnormalities in Clinical Laboratory Tests: Liver Tests
    Description The number of participants with an abnormal Liver function test. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN)
    Time Frame Up to 40 Months

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants with at least one treatment measure
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    ALT or AST > 3xULN
    0
    0%
    1
    7.7%
    1
    6.3%
    ALT or AST > 5xULN
    0
    0%
    0
    0%
    0
    0%
    ALT or AST > 10xULN
    0
    0%
    0
    0%
    0
    0%
    ALT or AST > 20xULN
    0
    0%
    0
    0%
    0
    0%
    Total Bilirubin (Tbili) > 2xULN
    0
    0%
    1
    7.7%
    1
    6.3%
    ALT or AST > 3xULN w/ Tbili > 2xULN within 1 day
    0
    0%
    1
    7.7%
    0
    0%
    ALT or AST > 3xULN w/ Tbili > 2xULN within 30 days
    0
    0%
    1
    7.7%
    0
    0%
    6. Primary Outcome
    Title Incidence of Laboratory Abnormalities in Specific Thyroid Tests
    Description Free T3 (FT3) Free T4 (FT4) Lower Limit of Normal (LLN)
    Time Frame Up to 40 Months

    Outcome Measure Data

    Analysis Population Description
    All Treated Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 13 16
    TSH > ULN
    0
    4
    4
    TSH > ULN: WITH TSH ≤ ULN AT BASELINE
    0
    3
    3
    TSH > ULN: WITH AT LEAST ONE FT3/FT4 TEST < LLN
    0
    2
    1
    TSH > ULN: WITH ALL OTHER FT3/FT4 TEST ≥ LLN
    0
    1
    1
    TSH > ULN: WITH FT3/FT4 TEST MISSING
    0
    1
    2
    TSH > 2*ULN
    0
    2
    1
    TSH > 2*ULN: WITH TSH <= ULN AT BASELINE
    0
    1
    0
    TSH > 2*ULN: WITH AT LEAST ONE FT3/FT4 TEST < LLN
    0
    2
    1
    TSH > 2*ULN: WITH ALL OTHER FT3/FT4 TEST ≥ LLN
    0
    0
    0
    TSH > 2*ULN: WITH FT3/FT4 TEST MISSING
    0
    0
    0
    TSH < LLN
    0
    3
    1
    TSH < LLN: WITH TSH >= LLN AT BASELINE
    0
    3
    1
    TSH < LLN: WITH AT LEAST ONE FT3/FT4 TEST > ULN
    0
    0
    1
    TSH < LLN: WITH ALL OTHER FT3/FT4 TEST ≤ ULN
    0
    1
    0
    TSH < LLN: WITH FT3/FT4 TEST MISSING
    0
    2
    0
    7. Secondary Outcome
    Title Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-CP no prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 2
    MMR Rate by 6 Months
    100
    5000%
    0
    0%
    MMR Rate by 12 Months
    100
    5000%
    0
    0%
    MMR Rate by 24 Months
    100
    5000%
    0
    0%
    MMR Rate by 36 Months
    100
    5000%
    0
    0%
    8. Secondary Outcome
    Title Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-CP prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 8 11
    MMR Rate by 6 Months
    0
    25
    18.2
    MMR Rate by 12 Months
    0
    25
    27.3
    MMR Rate by 24 Months
    0
    25
    36.4
    MMR Rate by 36 Months
    0
    25.0
    45.5
    9. Secondary Outcome
    Title Rate of Major Molecular Response (MMR) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). MMR is defined as ≥ 3-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.1% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 4 3
    MMR Rate by 6 Months
    0
    33.3
    MMR Rate by 12 Months
    0
    66.7
    MMR Rate by 24 Months
    0
    66.7
    MMR Rate by 36 Months
    0
    66.7
    10. Secondary Outcome
    Title Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), No Prior Dasatinib Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-CP no prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 2
    MR4.5 Rate by 6 Months
    0.0
    0.0
    MR4.5 Rate by 12 Months
    0.0
    0.0
    MR4.5 Rate by 24 Months
    0.0
    0.0
    MR4.5 Rate by 36 Months
    100
    0.0
    11. Secondary Outcome
    Title Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Chronic Phase (CML-CP), Prior Dasatinib Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-CP prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 8 11
    MR4.5 Rate by 6 Months
    0
    0.0
    0.0
    MR4.5 Rate by 12 Months
    0
    0.0
    0.0
    MR4.5 Rate by 24 Months
    0
    0.0
    0.0
    MR4.5 Rate by 36 Months
    0
    0.0
    0.0
    12. Secondary Outcome
    Title Rate of Molecular Response 4.5 (MR4.5) : Chronic Myelogenous Leukemia - Advanced Phase (CML-AP) Participants
    Description Molecular response was assessed using BCR-ABL transcript levels measurement by real-time quantitative polymerase chain reaction (RQ-PCR). A molecular response 4.5 (MR4.5) was defined as ≥ 4.5-log reduction in BCR-ABL transcripts or a ratio of ≤ 0.00316% on the International Scale (IS).
    Time Frame upto 36 Months

    Outcome Measure Data

    Analysis Population Description
    All treated Participants, CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 4 3
    MR4.5 Rate by 6 Months
    0.0
    0.0
    MR4.5 Rate by 12 Months
    0.0
    0.0
    MR4.5 Rate by 24 Months
    0.0
    0.0
    MR4.5 Rate by 36 Months
    0.0
    0.0
    13. Secondary Outcome
    Title Time to Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants
    Description measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP No Prior Dasatinib Subjects
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 2
    Median (95% Confidence Interval) [Months]
    0.53
    NA
    14. Secondary Outcome
    Title Time to Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants
    Description measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP Prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 8 11
    Median (95% Confidence Interval) [Months]
    NA
    NA
    35.45
    15. Secondary Outcome
    Title Time to Major Molecular Response (MMR) - CML-AP Participants
    Description measured from the date of first dosing until measurement criteria are first met for MMR. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 4 3
    Median (95% Confidence Interval) [Months]
    NA
    5.54
    16. Secondary Outcome
    Title Duration of Major Molecular Response (MMR) - CML-CP No Prior Dasatinib Participants
    Description will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP No Prior Dasatinib participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 0
    Median (95% Confidence Interval) [Months]
    NA
    17. Secondary Outcome
    Title Duration of Major Molecular Response (MMR) - CML-CP Prior Dasatinib Participants
    Description will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP Prior Dasatinib Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 2 5
    Median (95% Confidence Interval) [Months]
    NA
    NA
    18. Secondary Outcome
    Title Duration of Major Molecular Response (MMR) - CML-AP Participants
    Description will be computed for participants who have achieved MMR. It will be defined as the time from the first assessment in which MMR, is documented until the first assessment at which disease progression (or confirmed loss of MMR) is documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 0 2
    Median (95% Confidence Interval) [Months]
    NA
    19. Secondary Outcome
    Title Time to Molecular Response 4.5(MR4.5) - CML-CP No Prior Dasatinib Participants
    Description measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP No Prior Dasatinib Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 2
    Median (95% Confidence Interval) [Months]
    35.25
    NA
    20. Secondary Outcome
    Title Time to Molecular Response 4.5(MR4.5) - CML-CP Prior Dasatinib Participants
    Description measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP Prior Dasatinib Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 2 8 11
    Median (95% Confidence Interval) [Months]
    NA
    NA
    NA
    21. Secondary Outcome
    Title Time to Molecular Response 4.5(MR4.5) - CML-AP Participants
    Description measured from the date of first dosing until measurement criteria are first met for MR4.5. The participants who do not respond will be censored on the date of their last molecular assessment. It is defined for all treated participants.
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 4 3
    Median (95% Confidence Interval) [Months]
    NA
    NA
    22. Secondary Outcome
    Title Duration of Molecular Response 4.5 (MR4.5) - CML-CP No Prior Dasatinib Participants
    Description will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP No Prior Dasatinib Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 1 0
    Median (95% Confidence Interval) [Months]
    NA
    23. Secondary Outcome
    Title Duration of Molecular Response 4.5 (MR4.5) - CML-CP Prior Dasatinib Participants
    Description will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-CP Prior Dasatinib Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 0 0
    24. Secondary Outcome
    Title Duration of Molecular Response 4.5 (MR4.5) - CML-AP Participants
    Description will be computed for participants who have achieved MR4.5. It will be defined as the time from the first assessment in which MR4.5, is documented until the first assessment at which disease progression (or confirmed loss of MR4.5 documented. Participants who neither progress nor die will be censored on the date of their last molecular assessment
    Time Frame Up to 36 Months

    Outcome Measure Data

    Analysis Population Description
    CML-AP Participants
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    Measure Participants 0 0 0

    Adverse Events

    Time Frame Initiation of study drug to within 100 days of discontinuation of nivolumab dosing and 30 days of dasatinib dosing
    Adverse Event Reporting Description
    Arm/Group Title Dasatinib Only Dose Level 1 Dose Level 2
    Arm/Group Description dasatinib 100 mg QD(CP) or 140 mg QD (AP) Nivolumab 1 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP) Nivolumab 3 mg/kg q 2 weeks + dasatinib 100 mg QD (CP) or 140 mg QD (AP)
    All Cause Mortality
    Dasatinib Only Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Serious Adverse Events
    Dasatinib Only Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/2 (0%) 7/13 (53.8%) 8/16 (50%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Gastrointestinal disorders
    Abdominal pain upper 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Gastrointestinal haemorrhage 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Nausea 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    General disorders
    Device related thrombosis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Influenza like illness 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Hepatobiliary disorders
    Cholelithiasis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Infections and infestations
    Bronchiolitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Epiglottitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Septic shock 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Injury, poisoning and procedural complications
    Subdural haematoma 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Investigations
    Lipase increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    White blood cell count increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Adenocarcinoma of colon 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Blast crisis in myelogenous leukaemia 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Nervous system disorders
    Cerebral ischaemia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Facial paralysis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Syncope 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Other (Not Including Serious) Adverse Events
    Dasatinib Only Dose Level 1 Dose Level 2
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/2 (50%) 13/13 (100%) 16/16 (100%)
    Blood and lymphatic system disorders
    Anaemia 0/2 (0%) 4/13 (30.8%) 4/16 (25%)
    Neutropenia 0/2 (0%) 2/13 (15.4%) 4/16 (25%)
    Thrombocytopenia 0/2 (0%) 3/13 (23.1%) 4/16 (25%)
    Leukopenia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Lymphadenitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Lymphadenopathy 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Normochromic normocytic anaemia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Pancytopenia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Cardiac disorders
    Bundle branch block right 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Sinus bradycardia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Tachycardia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Ventricular extrasystoles 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Ear and labyrinth disorders
    Ear pain 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Vertigo 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Ear discomfort 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Hypoacusis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Tinnitus 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Endocrine disorders
    Hypothyroidism 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Eye disorders
    Conjunctivitis allergic 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Eyelid oedema 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Glaucoma 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Lacrimation increased 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Vision blurred 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/2 (0%) 1/13 (7.7%) 2/16 (12.5%)
    Constipation 0/2 (0%) 3/13 (23.1%) 2/16 (12.5%)
    Diarrhoea 0/2 (0%) 6/13 (46.2%) 7/16 (43.8%)
    Dyspepsia 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Faeces discoloured 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Nausea 0/2 (0%) 3/13 (23.1%) 6/16 (37.5%)
    Vomiting 0/2 (0%) 4/13 (30.8%) 6/16 (37.5%)
    Abdominal discomfort 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Abdominal distension 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Breath odour 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Chapped lips 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Diverticulum 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Flatulence 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Food poisoning 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Gastrooesophageal reflux disease 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Haemorrhoids 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Intestinal ischaemia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Large intestine polyp 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Rectal haemorrhage 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Tongue oedema 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Toothache 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    General disorders
    Asthenia 0/2 (0%) 5/13 (38.5%) 1/16 (6.3%)
    Chest pain 0/2 (0%) 2/13 (15.4%) 1/16 (6.3%)
    Chills 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Discomfort 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Face oedema 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Fatigue 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Mucosal inflammation 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Oedema 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Oedema peripheral 0/2 (0%) 2/13 (15.4%) 2/16 (12.5%)
    Pyrexia 0/2 (0%) 5/13 (38.5%) 2/16 (12.5%)
    Axillary pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Catheter site pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Gait disturbance 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    General physical health deterioration 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Generalised oedema 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Implant site pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Malaise 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Necrosis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Pain 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Peripheral swelling 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Temperature regulation disorder 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Thirst 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Hepatobiliary disorders
    Cholestasis 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Cholelithiasis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Hepatic function abnormal 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Hepatomegaly 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Immune system disorders
    Hypersensitivity 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Seasonal allergy 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Infections and infestations
    Nasopharyngitis 0/2 (0%) 2/13 (15.4%) 4/16 (25%)
    Oral herpes 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Rhinitis 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Upper respiratory tract infection 0/2 (0%) 5/13 (38.5%) 3/16 (18.8%)
    Urinary tract infection 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Abscess 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Campylobacter gastroenteritis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Chronic sinusitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Cytomegalovirus colitis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Epiglottitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Folliculitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Gastroenteritis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Gastroenteritis viral 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Helicobacter gastritis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Hordeolum 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Infection 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Laryngitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Periodontitis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Pharyngeal abscess 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Pharyngitis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Pneumonia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Pulpitis dental 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Sinusitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Skin infection 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Tooth abscess 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Viral infection 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Viral upper respiratory tract infection 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Wound infection bacterial 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Injury, poisoning and procedural complications
    Contusion 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Fall 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Face injury 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Joint dislocation 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Post procedural haemorrhage 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Post-traumatic pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Procedural pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Sunburn 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Wound complication 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Wound secretion 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Investigations
    Alanine aminotransferase increased 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Aspartate aminotransferase increased 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Blood creatinine increased 0/2 (0%) 2/13 (15.4%) 2/16 (12.5%)
    Neutrophil count decreased 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Platelet count decreased 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Weight decreased 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Blood phosphorus decreased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Blood potassium decreased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Blood sodium decreased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Blood thyroid stimulating hormone decreased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Blood thyroid stimulating hormone increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Cardiac murmur 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Lipase increased 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Serum ferritin decreased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Spleen palpable 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Thyroxine increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Tri-iodothyronine increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Weight increased 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 0/2 (0%) 1/13 (7.7%) 4/16 (25%)
    Hypokalaemia 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Hypomagnesaemia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Hypophosphataemia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Back pain 0/2 (0%) 3/13 (23.1%) 2/16 (12.5%)
    Bone pain 0/2 (0%) 3/13 (23.1%) 1/16 (6.3%)
    Groin pain 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Muscle spasms 1/2 (50%) 2/13 (15.4%) 1/16 (6.3%)
    Musculoskeletal pain 0/2 (0%) 2/13 (15.4%) 2/16 (12.5%)
    Pain in extremity 0/2 (0%) 3/13 (23.1%) 2/16 (12.5%)
    Facet joint syndrome 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Intervertebral disc protrusion 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Muscular weakness 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Musculoskeletal chest pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Musculoskeletal discomfort 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Myalgia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Neck pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Spondylolisthesis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Synovial cyst 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Tendonitis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Vertebral foraminal stenosis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Colon adenoma 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Nervous system disorders
    Dizziness 0/2 (0%) 3/13 (23.1%) 3/16 (18.8%)
    Headache 0/2 (0%) 4/13 (30.8%) 5/16 (31.3%)
    Paraesthesia 0/2 (0%) 2/13 (15.4%) 1/16 (6.3%)
    Carpal tunnel syndrome 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Dysgeusia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Facial paralysis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Hemiparesis 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Hypoaesthesia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Migraine 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Monoparesis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Peripheral sensory neuropathy 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Resting tremor 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Sciatica 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Syncope 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Psychiatric disorders
    Insomnia 0/2 (0%) 2/13 (15.4%) 1/16 (6.3%)
    Anxiety 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Depression 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Disorientation 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Panic attack 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Renal and urinary disorders
    Dysuria 0/2 (0%) 3/13 (23.1%) 0/16 (0%)
    Pollakiuria 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Urinary incontinence 0/2 (0%) 3/13 (23.1%) 0/16 (0%)
    Chromaturia 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Haematuria 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Urethral haemorrhage 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Urinary tract discomfort 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Reproductive system and breast disorders
    Testicular pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/2 (0%) 6/13 (46.2%) 2/16 (12.5%)
    Dyspnoea 0/2 (0%) 3/13 (23.1%) 1/16 (6.3%)
    Epistaxis 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Nasal congestion 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Oropharyngeal pain 0/2 (0%) 1/13 (7.7%) 3/16 (18.8%)
    Productive cough 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Bronchospasm 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Dyspnoea exertional 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Emphysema 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Orthopnoea 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Pharyngeal oedema 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Pleural effusion 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Pleuritic pain 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Pneumonitis 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Skin and subcutaneous tissue disorders
    Ecchymosis 0/2 (0%) 1/13 (7.7%) 1/16 (6.3%)
    Hyperhidrosis 0/2 (0%) 2/13 (15.4%) 0/16 (0%)
    Pruritus 0/2 (0%) 3/13 (23.1%) 0/16 (0%)
    Rash 0/2 (0%) 2/13 (15.4%) 5/16 (31.3%)
    Rash pruritic 0/2 (0%) 2/13 (15.4%) 1/16 (6.3%)
    Alopecia 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Angioedema 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Dermal cyst 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Dermatitis contact 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Drug eruption 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Dry skin 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Erythema 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Papule 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Petechiae 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Rash erythematous 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Rash papular 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Skin discolouration 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Skin lesion 0/2 (0%) 0/13 (0%) 1/16 (6.3%)
    Urticaria 0/2 (0%) 1/13 (7.7%) 0/16 (0%)
    Vascular disorders
    Hot flush 0/2 (0%) 0/13 (0%) 2/16 (12.5%)
    Hypertension 0/2 (0%) 1/13 (7.7%) 2/16 (12.5%)
    Hypotension 0/2 (0%) 1/13 (7.7%) 2/16 (12.5%)
    Haematoma 0/2 (0%) 1/13 (7.7%) 0/16 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Bristol-Myers Squibb Study Director
    Organization Bristol-Myers squibb
    Phone Please Email
    Email Clinical.Trials@BMS.com
    Responsible Party:
    Bristol-Myers Squibb
    ClinicalTrials.gov Identifier:
    NCT02011945
    Other Study ID Numbers:
    • CA180-373
    • 2013-002156-33
    First Posted:
    Dec 16, 2013
    Last Update Posted:
    Mar 18, 2020
    Last Verified:
    Feb 1, 2020