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

A Phase II Study to Determine the Activity of Dasatinib Administered Orally (PO) at a Dose of 100 mg Once Daily (QD) in Chronic Phase Chronic Myelogenous Leukemia (CML), at a Dose of 70 mg Twice Daily (BID) in Advanced Phase Chronic Myelogenous Leukemia (CML) Chinese Subjects Who Are Resistant to or Intolerant of Imatinib Mesylate (Gleevec®)

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00529763

Enrollment

121

Registered

2007-09-14

Start date

2007-11-17

Completion date

2022-04-20

Last updated

2023-05-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leukemia

Keywords

Chronic Phase, Advanced Phase chronic myeloid leukemia, Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Brief summary

The primary objective of this study is to estimate the major cytogenetic response (MCyR) rate to Dasatinib in subjects with CP CML, complete and overall hematologic response (CHR and OHR) rate in subjects with AD CML or Ph+ ALL who have primary or acquired resistance to imatinib, or are intolerant of imatinib, when administered at 100 mg QD (Chronic CML) or 70mg BID (AP CML and Ph+ALL).

Interventions

DRUGDasatinib

Tablets, Oral, 70 mg BID (AD CML) or 100 mg QD (Chronic CML), once or twice daily dependent on disease stage, until subjects meet discontinuation (DC) criteria for study

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Signed Written Informed Consent * Men and women, ages 18 years of age or older * Subjects with Chronic Phase (CP) or Advanced Disease (AD) chronic myeloid leukemia (CML)/Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) * Subjects resistant/intolerant to imatinib * Subjects presenting: 1. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0-2 2. Adequate hepatic function 3. Adequate renal function 4. Sodium, Potassium, Magnesium, Phosphorus, Calcium higher or equal than the lower limit of normal range

Exclusion criteria

* Women of child bearing potential who are not using adequate birth control * Women who are pregnant or breastfeeding * Subjects eligible for stem cell transplantation * Serious uncontrolled medical disorder or active infection * Uncontrolled or significant cardiovascular disease * Concurrent incurable malignancy other than CML * Subjects who received imatinib, interferon, cytarabine within 7 days or other antineoplastic agents other than hydroxyurea within 14 days before dasatinib, Dasatinib in the past * History of significant bleeding unrelated to CML

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)	From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)	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 \[BM\].
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)	From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)	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)

Secondary

Measure	Time frame	Description
Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants	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])	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).
Progression-free Survival Among CP CML Participants	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])	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.
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)	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])	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.
Duration of CHR Among AD CML and Ph+ ALL Participants	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])	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.
Duration of MaHR Among AD CML and Ph+ ALL Participants	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])	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.
Progression-free Survival Among AD CML and Ph+ ALL Participants	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])	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.
Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Complete Hematologic Response (CHR)	From first dose up to approximately 12 months of follow up after dasatinib treatment (data cut-off date: 18-Jun-2010)	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.
Mean Dasatinib Plasma Concentrations	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),	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
Mean Maximum Concentration (Cmax) of Dasatinib Following 70 mg BID and 100 QD Dose Administration	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)	Cmax=maximum observed plasma concentration of dasatinib
Mean (Tmax) and (T-Half) of Dasatinib Following 70 mg BID and 100 QD Dose Administration	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)	Tmax=time of maximum observed plasma concentration. T-Half=plasma half-life.
Mean (AUC[0-T]), (AUC[INF]), and (AUC[TAU])of Dasatinib Following 70 mg BID and 100 QD Dose Administration	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)	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
Mean Oral Clearance (CLo) of Dasatinib Following 70 mg BID and 100 QD Dose Administration	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)	—
Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration	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)	—
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	From first dose to 30 days after last dose. (Up to approximately 161 months)	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.
Time to Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants	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])	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).

Countries

China

Participant flow

Participants by arm

Arm	Count
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.	25
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.	37
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.	59
Total	121

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
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	Other reasons	2	0	2
Overall Study	Participant request to discontinue treatment	1	1	3
Overall Study	Participant Withdrew Consent	2	3	4
Overall Study	Stem Cell Transplant	0	3	1
Overall Study	Study Drug Toxicity	3	6	4

Baseline characteristics

Characteristic	Advanced Disease CML - Accelerated Phase (AP)	Advanced Disease CML - Blast Phase/PH+ ALL	Chronic Phase (CP) CML	Total
Age, Continuous	39.5 years STANDARD_DEVIATION 10.5	39.2 years STANDARD_DEVIATION 13.4	42.8 years STANDARD_DEVIATION 11.3	41.0 years STANDARD_DEVIATION 11.9
Age, Customized <=21 years	1 Participants	4 Participants	2 Participants	7 Participants
Age, Customized Between 21 and 45 years	18 Participants	23 Participants	33 Participants	74 Participants
Age, Customized Between 46 and 65 years	5 Participants	9 Participants	23 Participants	37 Participants
Age, Customized Between 66 and 75 years	1 Participants	1 Participants	1 Participants	3 Participants
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 0	8 units on a scale	2 units on a scale	25 units on a scale	35 units on a scale
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 1	16 units on a scale	29 units on a scale	33 units on a scale	78 units on a scale
Eastern co-operative Oncology Group Performance Status (ECOG PS) ECOG PS = 2	1 units on a scale	6 units on a scale	0 units on a scale	7 units on a scale
Eastern co-operative Oncology Group Performance Status (ECOG PS) Not Reported	0 units on a scale	0 units on a scale	1 units on a scale	1 units on a scale
Race/Ethnicity, Customized Asian	25 Participants	37 Participants	59 Participants	121 Participants
Region of Enrollment China China	25 Participants	37 Participants	59 Participants	121 Participants
Sex: Female, Male Female	10 Participants	9 Participants	23 Participants	42 Participants
Sex: Female, Male Male	15 Participants	28 Participants	36 Participants	79 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	5 / 25	16 / 37	5 / 59
other Total, other adverse events	24 / 25	30 / 37	50 / 59
serious Total, serious adverse events	13 / 25	24 / 37	18 / 59

Outcome results

Primary

Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)

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 \[BM\].

Time frame: 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.

Arm	Measure	Value (NUMBER)
Chronic Phase (CP) CML	Percentage of Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants With Major Cytogenetic Response (MCyR)	50.8 Percentage of participants

Primary

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)

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)

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	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
Advanced Disease CML - 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	16.2 Percentage of participants
Advanced Disease CML - 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)	MaHR	29.7 Percentage of participants
Advanced Disease CML - 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)	OHR	35.1 Percentage of participants

Secondary

Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest

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.

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

Population: All treated participants

Arm	Measure	Group	Value (NUMBER)
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All AEs	52 Participants
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related AEs	46 Participants
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Oedema	0 Participants
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related Gr3/4 AEs	14 Participants
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All-Causality SAEs	18 Participants
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related SAEs	10 Participants
Chronic Phase (CP) CML	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
Chronic Phase (CP) CML	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Deaths	4 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Pulmonary Hypertension	3 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Deaths	4 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All-Causality SAEs	13 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related SAEs	8 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All-Causality AEs Leading to Discontinuation	9 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related AEs leading to Discontinuation	3 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All AEs	25 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related AEs	21 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related Gr3/4 AEs	16 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	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	0 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Pleural Effusion	13 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Oedema Peripheral	1 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Pericardial Effusion	5 Participants
Advanced Disease CML - Blast Phase/PH+ ALL	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Oedema	2 Participants
Total	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
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Pleural Effusion	10 Participants
Total	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
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All-Causality AEs Leading to Discontinuation	19 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Pulmonary Hypertension	0 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related SAEs	11 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Deaths	13 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Oedema Peripheral	0 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All-Causality SAEs	24 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related Gr3/4 AEs	21 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-Related AEs	30 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	Drug-related FR AE - Oedema	1 Participants
Total	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	0 Participants
Total	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Drug-related Fluid Retention AEs of Special Interest	All AEs	33 Participants

Secondary

Duration of CHR Among AD CML and Ph+ ALL Participants

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.

Time frame: 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.

Arm	Measure	Value (NUMBER)
Chronic Phase (CP) CML	Duration of CHR Among AD CML and Ph+ ALL Participants	NA Months
Advanced Disease CML - Blast Phase/PH+ ALL	Duration of CHR Among AD CML and Ph+ ALL Participants	NA Months

Secondary

Duration of MaHR Among AD CML and Ph+ ALL Participants

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.

Time frame: 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.

Arm	Measure	Value (NUMBER)
Chronic Phase (CP) CML	Duration of MaHR Among AD CML and Ph+ ALL Participants	NA Months
Advanced Disease CML - Blast Phase/PH+ ALL	Duration of MaHR Among AD CML and Ph+ ALL Participants	11.2 Months

Secondary

Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants

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).

Time frame: 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.

Arm	Measure	Value (NUMBER)
Chronic Phase (CP) CML	Duration of Major Cytogenetic Response (MCyR) in Chronic Phase Chronic Myeloid Leukemia (CP - CML) Participants	NA Months

Secondary

Mean Apparent Volume of Distribution (Vz/F) of Dasatinib Following 70 mg BID and 100 QD Dose Administration

Time frame: 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)