Trial Outcomes & Findings for Dasatinib in Imatinib Resistant/Intolerant Chinese CML (Chronic and Advanced Phase) Subjects (NCT NCT00529763)

NCT ID: NCT00529763

Last Updated: 2023-05-08

Results Overview

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR) or Partial Cytogenetic Response (PCyR). CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow \[BM\] PCyR: 1-35% Ph-chromosome-positive cells in metaphase in \[BM\].

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 121 participants
• Primary outcome timeframe: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)
• Results posted on: 2023-05-08

Participant Flow

Participant milestones

Measure	Advanced Disease CML - Accelerated Phase (AP) Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Chronic Phase (CP) CML Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.
Overall Study STARTED	25	37	59
Overall Study COMPLETED	4	0	27
Overall Study NOT COMPLETED	21	37	32

Reasons for withdrawal

Measure	Advanced Disease CML - Accelerated Phase (AP) Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Chronic Phase (CP) CML Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.
Overall Study Adverse Event Unrelated to Study Drug	1	5	3
Overall Study Death	1	1	1
Overall Study Disease Progression	10	16	11
Overall Study Lost to Follow-up	1	2	3
Overall Study Stem Cell Transplant	0	3	1
Overall Study Study Drug Toxicity	3	6	4
Overall Study Participant Withdrew Consent	2	3	4
Overall Study Other reasons	2	0	2
Overall Study Participant request to discontinue treatment	1	1	3

Baseline Characteristics

Dasatinib in Imatinib Resistant/Intolerant Chinese CML (Chronic and Advanced Phase) Subjects

Baseline characteristics by cohort

Measure	Advanced Disease CML - Accelerated Phase (AP) n=25 Participants Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=37 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Chronic Phase (CP) CML n=59 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total n=121 Participants Total of all reporting groups
Age, Customized Between 21 and 45 years	18 Participants n=5 Participants	23 Participants n=7 Participants	33 Participants n=5 Participants	74 Participants n=4 Participants
Age, Customized Between 46 and 65 years	5 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants	37 Participants n=4 Participants
Age, Continuous	39.5 years STANDARD_DEVIATION 10.5 • n=5 Participants	39.2 years STANDARD_DEVIATION 13.4 • n=7 Participants	42.8 years STANDARD_DEVIATION 11.3 • n=5 Participants	41.0 years STANDARD_DEVIATION 11.9 • n=4 Participants
Age, Customized <=21 years	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Age, Customized Between 66 and 75 years	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants	42 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	28 Participants n=7 Participants	36 Participants n=5 Participants	79 Participants n=4 Participants
Race/Ethnicity, Customized Asian	25 Participants n=5 Participants	37 Participants n=7 Participants	59 Participants n=5 Participants	121 Participants n=4 Participants
Region of Enrollment China · China	25 Participants n=5 Participants	37 Participants n=7 Participants	59 Participants n=5 Participants	121 Participants n=4 Participants
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 0	8 units on a scale n=5 Participants	2 units on a scale n=7 Participants	25 units on a scale n=5 Participants	35 units on a scale n=4 Participants
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 1	16 units on a scale n=5 Participants	29 units on a scale n=7 Participants	33 units on a scale n=5 Participants	78 units on a scale n=4 Participants
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 2	1 units on a scale n=5 Participants	6 units on a scale n=7 Participants	0 units on a scale n=5 Participants	7 units on a scale n=4 Participants
Eastern co-operative Oncology Group Performance Status (ECOG PS) Not Reported	0 units on a scale n=5 Participants	0 units on a scale n=7 Participants	1 units on a scale n=5 Participants	1 units on a scale n=4 Participants

PRIMARY outcome

Timeframe: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)

Population: All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML). Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR) or Partial Cytogenetic Response (PCyR).

CCyR: 0% Ph-chromosome-positive cells in metaphase in bone marrow [BM] PCyR: 1-35% Ph-chromosome-positive cells in metaphase in [BM].

Outcome measures

Measure	Chronic Phase (CP) CML n=59 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)	50.8 Percentage of participants Interval 37.5 to 64.1	—	—

PRIMARY outcome

Timeframe: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)

Population: All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML). Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL).

CHR=white blood cells (WBC) ≤upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, <20% basophils & <5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 & <100,000/mm3; ANC >500/mm3 & <1,000/mm3.

Overall hematologic response (OHR)=CHR+NEL+ return to chronic phase (RTC=<15% blasts in BM and PB; <30% blasts+promyelocytes in BM & PB; <20% basophils in PB; no extra-medullar disease other than spleen & liver)

Outcome measures

Measure	Chronic Phase (CP) CML n=25 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=37 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Percentage of Participants With Complete, Major, and Overall Hematologic Response (CHR, MaHR, & OHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Blast Phase CML/Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) CHR	52.0 Percentage of participants Interval 31.3 to 72.2	16.2 Percentage of participants Interval 6.2 to 32.0	—
Percentage of Participants With Complete, Major, and Overall Hematologic Response (CHR, MaHR, & OHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Blast Phase CML/Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) MaHR	84.0 Percentage of participants Interval 63.9 to 95.5	29.7 Percentage of participants Interval 15.9 to 47.0	—
Percentage of Participants With Complete, Major, and Overall Hematologic Response (CHR, MaHR, & OHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Blast Phase CML/Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) OHR	92.0 Percentage of participants Interval 74.0 to 99.0	35.1 Percentage of participants Interval 20.2 to 52.5	—

SECONDARY outcome

Timeframe: From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)

Population: All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML). Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Complete Hematologic Response (CHR) is obtained when all the following criteria are met: WBC ≤ institutional ULN; platelets ≤ 450,000/mm3; ≤20% basophils in peripheral blood; no blasts or promyelocytes in PB cells; < 5% myelocytes plus metamyelocytes in PB cells; no extra-medullary involvement including no hepatomegaly or splenomegaly.

Outcome measures

Measure	Chronic Phase (CP) CML n=59 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Complete Hematologic Response (CHR)	91.5 Percentage of participants Interval 81.3 to 97.2	—	—

SECONDARY outcome

Timeframe: From first dose up to the day criteria were first met for CCyR or PCyR, whichever occurred first. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML) with MCyR. Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Time to MCyR is defined as the time from the first dosing date until day criteria were first met for CCyR or PCyR, whichever occurred first.

Major Cytogenetic Response (MCyR) is defined as Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in BM) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in BM).

Outcome measures

Measure	Chronic Phase (CP) CML n=30 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Time to Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants	12.1 Weeks Interval 4.3 to 48.0	—	—

SECONDARY outcome

Timeframe: From first dose until the date of progression or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML) with MCyR. Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

The duration of time from when the first day all criteria are met for CCyR or PCyR until the date of progression or death. Participants who neither progress nor die will be censored on the date of their last cytogenetic assessment. The duration of MCyR will be estimated via the Kaplan-Meier product-limit method.

Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR: 0% Ph-chromosome-positive cells in metaphase in BM) or Partial Cytogenetic Response (PCyR: 1-35% Ph-chromosome-positive cells in metaphase in BM).

Outcome measures

Measure	Chronic Phase (CP) CML n=30 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants	NA Months Insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: From first dosing date until the time progressive disease (PD) is first documented. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Chronic Phase Chronic Myeloid Leukemia (CP - CML). Data pre-specified to be collected in the Chronic Phase (CP) CML arm only.

Progression-free survival is defined as the time from first dosing date until the time progressive disease (PD) is first documented. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who do not progress nor die will be censored on the date of their last hematologic or cytogenetic assessment, whichever comes last. PFS will be analyzed via the Kaplan-Meier product-limit method.

Participants were considered as having PD if they: achieved a hematologic response but subsequently no longer meet the criteria consistently on all assessment over a consecutive 2-week period after starting maximum dose; had no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period, or had an increase by at least 50% in PB blast count (absolute) over a 2-week period after starting their maximum (individually-tolerated) dose.

Outcome measures

Measure	Chronic Phase (CP) CML n=59 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Progression-free Survival Among CP CML Participants	NA Months Insufficient number of participants with events	—	—

SECONDARY outcome

Timeframe: From first dose of Dasatinib until the first day CHR criteria are met (for all confirmed responses). (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR or MaHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

The time from first dose of Dasatinib until the first day CHR or MaHR criteria are met (for all confirmed responses). Time to CHR is computed only for participants whose best response is CHR. Major HR (MaHR) includes CHR or no evidence of leukemia (NEL).

Major hematologic response: (MaHR) = complete hematologic response (CHR) + no evidence of leukemia (NEL).

CHR=white blood cells (WBC) ≤upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, <20% basophils & <5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 & <100,000/mm3; ANC >500/mm3 & <1,000/mm3.

Outcome measures

Measure	Chronic Phase (CP) CML n=21 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total n=32 Participants All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Time to Complete and Major Hematologic Response (CHR and MaHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Participants (Ph+ ALL) CHR	16.0 Weeks Interval 11.7 to 52.1	12.1 Weeks Interval 11.6 to 28.0	12.1 Weeks Interval 11.6 to 52.1
Time to Complete and Major Hematologic Response (CHR and MaHR) in Advanced Disease Chronic Myeloid Leukemia (AD CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Participants (Ph+ ALL) MaHR	12.1 Weeks Interval 11.7 to 28.6	12.1 Weeks Interval 11.6 to 24.0	12.1 Weeks Interval 11.6 to 28.6

SECONDARY outcome

Timeframe: From first dose until the date of disease progression (PD) or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Time from the first day all criteria are met for CHR until the date treatment is discontinued due to progressive disease (PD) or death. Participants who neither progress nor die will be censored on the date of their last assessment.

CHR=white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, <20% basophils and <5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

PD = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

Outcome measures

Measure	Chronic Phase (CP) CML n=13 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=6 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Duration of CHR Among AD CML and Ph+ ALL Participants	NA Months Interval 17.2 to Insufficient number of participants with events	NA Months Interval 13.2 to Insufficient number of participants with events	—

SECONDARY outcome

Timeframe: From first dose until the date of disease progression (PD) or death. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML) with CHR or NEL or MiHR. Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Time from the first day all criteria are met for CHR or NEL or MaHR until the date of progression or death. Participants who neither progress nor die will be censored on the date of their last assessment.

MAHR = CHR or no evidence of leukemia (NEL). CHR=white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥1,000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes, <20% basophils and <5% myelocytes+metamyelocytes in peripheral blood (PB); BM blasts ≤5%; no extra-medullary involvement/hepatomegaly/splenomegaly.

NEL=CHR except platelets ≥20,000/mm3 and <100,000/mm3; ANC >500/mm3 and <1,000/mm3.

Progressive disease (PD) = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

Outcome measures

Measure	Chronic Phase (CP) CML n=21 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Duration of MaHR Among AD CML and Ph+ ALL Participants	NA Months Interval 22.9 to Insufficient number of participants with events	11.2 Months Interval 2.8 to Insufficient number of participants with events	—

SECONDARY outcome

Timeframe: From first dose until the time progressive disease (PD) is first documented. (Up to approximately 12 months of follow up after dasatinib treatment [data cut-off date: 18-Jun-2010])

Population: All treated participants with Advanced Disease Chronic Myeloid Leukemia (CML). Data pre-specified to be collected in the Advanced Disease CML - AP and Blast Phase/PH+ ALL arms only.

Progression-free survival is defined as the time from first dosing date until the time progressive disease (PD) is first documented. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who do not progress nor die will be censored on the date of their last hematologic or cytogenetic assessment whichever comes last. PFS will be analyzed via the Kaplan-Meier product-limit method.

Progressive disease (PD) = Hematologic response achieved but subsequently no longer meet the criteria consistently on all assessment over a 2-week period;, and no decrease from their baseline percent blasts in PB or BM on all assessments over a 4-week period or have an increase by at least 50% in PB blast count (absolute) over a 2-week period.

Outcome measures

Measure	Chronic Phase (CP) CML n=25 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=37 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Progression-free Survival Among AD CML and Ph+ ALL Participants	25.7 Months Interval 20.3 to Insufficient number of participants with events	4.3 Months Interval 2.6 to 7.4	—

SECONDARY outcome

Timeframe: From first dose to 30 days after last dose. (Up to approximately 161 months)

Population: All treated participants

AEs and SAEs considered possibly, probably, or certainly related to study treatment, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Death).SAE= any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent/significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.

Outcome measures

Measure	Chronic Phase (CP) CML n=59 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=25 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total n=37 Participants All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest All-Causality SAEs	18 Participants	13 Participants	24 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-Related SAEs	10 Participants	8 Participants	11 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest All-Causality AEs Leading to Discontinuation	10 Participants	9 Participants	19 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-Related AEs	46 Participants	21 Participants	30 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-Related Gr3/4 AEs	14 Participants	16 Participants	21 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related Fluid Retention-related AEs (FR AE) - Ascites	2 Participants	0 Participants	0 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related FR AE - Pleural Effusion	16 Participants	13 Participants	10 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related FR AE - Pulmonary Hypertension	5 Participants	3 Participants	0 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related FR AE - Oedema Peripheral	2 Participants	1 Participants	0 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related FR AE - Pericardial Effusion	2 Participants	5 Participants	2 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-related FR AE - Oedema	0 Participants	2 Participants	1 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Deaths	4 Participants	4 Participants	13 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest Drug-Related AEs leading to Discontinuation	6 Participants	3 Participants	6 Participants
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest All AEs	52 Participants	25 Participants	33 Participants

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Days 6 and 7 (0 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose),

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Mean dasatinib plasma concentrations following 70 mg BID dose in AD CML or Ph+ ALL participants and following 100 mg QD dose in CP CML participants

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean Dasatinib Plasma Concentrations Day 1: 0.5 hours postdose	56.74 ng/mL Standard Deviation 59.71	133.18 ng/mL Standard Deviation 116.06	—
Mean Dasatinib Plasma Concentrations Day 1 : 1 hour postdose	54.57 ng/mL Standard Deviation 44.06	130.86 ng/mL Standard Deviation 81.56	—
Mean Dasatinib Plasma Concentrations Day 1 : 2 hours postdose	29.50 ng/mL Standard Deviation 24.87	100.69 ng/mL Standard Deviation 60.37	—
Mean Dasatinib Plasma Concentrations Day 1 : 3 hours postdose	16.65 ng/mL Standard Deviation 12.23	64.90 ng/mL Standard Deviation 31.15	—
Mean Dasatinib Plasma Concentrations Day 1 : 4 hours postdose	12.02 ng/mL Standard Deviation 7.95	38.18 ng/mL Standard Deviation 16.48	—
Mean Dasatinib Plasma Concentrations Day 1 : 5 hours postdose	8.53 ng/mL Standard Deviation 4.51	26.33 ng/mL Standard Deviation 11.83	—
Mean Dasatinib Plasma Concentrations Day 1 : 6 hours postdose	7.37 ng/mL Standard Deviation 4.89	20.71 ng/mL Standard Deviation 9.91	—
Mean Dasatinib Plasma Concentrations Day 1 : 8 hours postdose	4.48 ng/mL Standard Deviation 2.21	14.00 ng/mL Standard Deviation 7.25	—
Mean Dasatinib Plasma Concentrations Day 1 : 12 hours postdose	2.42 ng/mL Standard Deviation 0.93	6.57 ng/mL Standard Deviation 3.82	—
Mean Dasatinib Plasma Concentrations Day 1 : 24 hours postdose	1.07 ng/mL Standard Deviation 0.08	2.59 ng/mL Standard Deviation 1.43	—
Mean Dasatinib Plasma Concentrations Day 6: 0 hours postdose	8.93 ng/mL Standard Deviation 4.24	3.15 ng/mL Standard Deviation 3.57	—
Mean Dasatinib Plasma Concentrations Day 7: 0 hours postdose	8.77 ng/mL Standard Deviation 4.40	3.02 ng/mL Standard Deviation 2.03	—
Mean Dasatinib Plasma Concentrations Day 8: 0 hours postdose	8.22 ng/mL Standard Deviation 3.41	2.75 ng/mL Standard Deviation 1.58	—
Mean Dasatinib Plasma Concentrations Day 8: 0.5 hours postdose	48.74 ng/mL Standard Deviation 56.24	102.69 ng/mL Standard Deviation 92.00	—
Mean Dasatinib Plasma Concentrations Day 8: 1 hours postdose	52.55 ng/mL Standard Deviation 39.79	168.51 ng/mL Standard Deviation 112.14	—
Mean Dasatinib Plasma Concentrations Day 8: 2 hours postdose	44.32 ng/mL Standard Deviation 31.31	102.05 ng/mL Standard Deviation 69.80	—
Mean Dasatinib Plasma Concentrations Day 8: 3 hours postdose	31.64 ng/mL Standard Deviation 19.93	71.23 ng/mL Standard Deviation 34.29	—
Mean Dasatinib Plasma Concentrations Day 8: 4 hours postdose	18.33 ng/mL Standard Deviation 9.66	45.17 ng/mL Standard Deviation 20.04	—
Mean Dasatinib Plasma Concentrations Day 8: 5 hours postdose	13.74 ng/mL Standard Deviation 6.36	31.16 ng/mL Standard Deviation 13.47	—
Mean Dasatinib Plasma Concentrations Day 8: 6 hours postdose	10.91 ng/mL Standard Deviation 5.09	23.62 ng/mL Standard Deviation 12.13	—
Mean Dasatinib Plasma Concentrations Day 8: 8 hours postdose	7.23 ng/mL Standard Deviation 3.28	15.41 ng/mL Standard Deviation 8.04	—
Mean Dasatinib Plasma Concentrations Day 8: 12 hours postdose	3.96 ng/mL Standard Deviation 1.62	7.55 ng/mL Standard Deviation 3.90	—

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Cmax=maximum observed plasma concentration of dasatinib

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean Maximum Concentration (Cmax) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 1	71.01 ng/mL Standard Deviation 54.705	170.53 ng/mL Standard Deviation 99.245	—
Mean Maximum Concentration (Cmax) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 8	71.54 ng/mL Standard Deviation 51.908	181.79 ng/mL Standard Deviation 94.689	—

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Tmax=time of maximum observed plasma concentration. T-Half=plasma half-life.

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Tmax: Day 1	1.17 hours Standard Deviation 1.348	1.50 hours Standard Deviation 0.947	—
Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Tmax: Day 8	1.62 hours Standard Deviation 0.896	1.23 hours Standard Deviation 0.684	—
Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration T-Half: Day 1	4.35 hours Standard Deviation 2.445	4.78 hours Standard Deviation 1.679	—
Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration T-Half: Day 8	4.80 hours Standard Deviation 1.660	5.71 hours Standard Deviation 1.012	—

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration AUC(0-T)for dasatinib. AUC(INF)=area under the plasma concentration-time curve from time zero extrapolated to infinite time. AUC(TAU)=area under the plasma concentration-time curve for a dosing interval

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(0-T): Day 8	214.60 ng*h/mL Standard Deviation 102.616	567.30 ng*h/mL Standard Deviation 286.851	—
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(INF): Day 1	174.26 ng*h/mL Standard Deviation 105.824	526.33 ng*h/mL Standard Deviation 216.351	—
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(0-T): Day 1	161.30 ng*h/mL Standard Deviation 104.266	505.73 ng*h/mL Standard Deviation 214.365	—
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(INF): Day 8	247.10 ng*h/mL Standard Deviation 103.802	588.52 ng*h/mL Standard Deviation 293.512	—
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(TAU): Day 1	163.56 ng*h/mL Standard Deviation 103.573	511.07 ng*h/mL Standard Deviation 211.781	—
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration AUC(TAU): Day 8	218.05 ng*h/mL Standard Deviation 104.156	568.85 ng*h/mL Standard Deviation 285.532	—

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean Oral Clearance (CLo) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 1	564.97 mL/h Standard Deviation 318.555	221.84 mL/h Standard Deviation 99.003	—
Mean Oral Clearance (CLo) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 8	441.08 mL/h Standard Deviation 307.574	211.09 mL/h Standard Deviation 88.089	—

SECONDARY outcome

Timeframe: Day 1 (0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24 hours postdose), Day 8 (0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12 hours postdose)

Population: All treated participants with evaluable PK data. Data collection pre-specified by treatment dosage.

Outcome measures

Measure	Chronic Phase (CP) CML n=11 Participants Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=11 Participants Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Total All treated Participants with Advanced Disease CML - Accelerated Phase (AP) and Blast Phase/PH+ ALL
Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 1	3785.78 mL/h Standard Deviation 3034.812	1454.71 mL/h Standard Deviation 604.728	—
Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration Day 8	3446.74 mL/h Standard Deviation 3196.014	1719.14 mL/h Standard Deviation 730.345	—

Adverse Events

Advanced Disease CML - Accelerated Phase (AP)

Serious events: 13 serious events

Other events: 24 other events

Deaths: 5 deaths

Advanced Disease CML - Blast Phase/PH+ ALL

Serious events: 24 serious events

Other events: 30 other events

Deaths: 16 deaths

Chronic Phase (CP) CML

Serious events: 18 serious events

Other events: 50 other events

Deaths: 5 deaths

Serious adverse events

Measure	Advanced Disease CML - Accelerated Phase (AP) n=25 participants at risk Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=37 participants at risk Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Chronic Phase (CP) CML n=59 participants at risk Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.
Blood and lymphatic system disorders Bone marrow necrosis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Blood and lymphatic system disorders Thrombocytopenia	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Cardiac disorders Cardiac failure	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Ascites	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Colitis ulcerative	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Diarrhoea	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Duodenal perforation	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Enteritis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Enterocolitis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Gastrointestinal haemorrhage	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Pancreatitis acute	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Upper gastrointestinal haemorrhage	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Death	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Fatigue	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Multiple organ dysfunction syndrome	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Oedema	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Pyrexia	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Sudden death	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Hepatobiliary disorders Cholelithiasis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Anal infection	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Bacterial sepsis	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Cellulitis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Enterococcal sepsis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Infection	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Klebsiella sepsis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Pneumonia	12.0% 3/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	16.2% 6/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Respiratory tract infection	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Sepsis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Septic shock	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Upper respiratory tract infection	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Injury, poisoning and procedural complications Peripheral nerve injury	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Osteonecrosis	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Blast crisis in myelogenous leukaemia	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central nervous system leukaemia	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia	20.0% 5/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	18.9% 7/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myeloid leukaemia transformation	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ureteric cancer	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Central nervous system haemorrhage	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Cerebral haemorrhage	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Haemorrhage intracranial	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Intracranial haematoma	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Renal and urinary disorders Acute kidney injury	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Renal and urinary disorders Renal failure	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Renal and urinary disorders Renal impairment	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pleural effusion	12.0% 3/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.8% 4/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	3.4% 2/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Surgical and medical procedures Allogenic bone marrow transplantation therapy	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Surgical and medical procedures Bone marrow transplant	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Vascular disorders Hypertension	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .

Other adverse events

Measure	Advanced Disease CML - Accelerated Phase (AP) n=25 participants at risk Participants with AP advanced disease CML who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Advanced Disease CML - Blast Phase/PH+ ALL n=37 participants at risk Participants with blast phase (BP) advanced disease CML or Philadelphia positive acute lymphoblastic leukemia (Ph+ALL) who received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 70 mg BID. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.	Chronic Phase (CP) CML n=59 participants at risk Participants with chronic phase (CP) CML who have received prior treatment with imatinib mesylate and can no longer be treated with this drug due to primary or acquired resistance or intolerance. Dasatinib was administered orally at a dose of 100 mg QD in patients with chronic phase CML. Participants were treated until progression of disease or intolerable toxicity as determined by the treating physician.
Blood and lymphatic system disorders Anaemia	12.0% 3/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.1% 3/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	16.9% 10/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Blood and lymphatic system disorders Febrile neutropenia	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Blood and lymphatic system disorders Leukopenia	16.0% 4/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Blood and lymphatic system disorders Neutropenia	28.0% 7/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.8% 4/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.5% 5/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Blood and lymphatic system disorders Thrombocytopenia	24.0% 6/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.8% 4/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	15.3% 9/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Cardiac disorders Palpitations	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Cardiac disorders Pericardial effusion	20.0% 5/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	3.4% 2/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Abdominal pain upper	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Constipation	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Diarrhoea	32.0% 8/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.8% 4/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Gastrointestinal haemorrhage	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.1% 3/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Gingival bleeding	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Gastrointestinal disorders Toothache	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Chest discomfort	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Fatigue	12.0% 3/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
General disorders Pyrexia	16.0% 4/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	21.6% 8/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	11.9% 7/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Hepatobiliary disorders Hyperbilirubinaemia	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.1% 3/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Infection	16.0% 4/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Laryngitis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Nasopharyngitis	12.0% 3/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Oral infection	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Pneumonia	32.0% 8/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	18.9% 7/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Infections and infestations Upper respiratory tract infection	20.0% 5/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.1% 3/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	10.2% 6/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Injury, poisoning and procedural complications Contusion	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Investigations Alanine aminotransferase increased	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.5% 5/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Investigations Aspartate aminotransferase increased	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	6.8% 4/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Metabolism and nutrition disorders Decreased appetite	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Arthralgia	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	1.7% 1/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Bone pain	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Dizziness	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	6.8% 4/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Nervous system disorders Headache	16.0% 4/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	23.7% 14/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Cough	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	8.5% 5/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.0% 1/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	6.8% 4/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pleural effusion	48.0% 12/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	24.3% 9/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	23.7% 14/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pneumonitis	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	6.8% 4/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	0.00% 0/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Skin and subcutaneous tissue disorders Rash	8.0% 2/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.4% 2/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	3.4% 2/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .
Vascular disorders Hypertension	0.00% 0/25 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	2.7% 1/37 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .	5.1% 3/59 • Participants were assessed for all-cause mortality from their first dose to their study completion (up to approximately 173 months). AE and SAEs were collected form first dose to 30 days post last dose (up to approximately 161 months) .

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER