Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemic Study

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00978731
• Collaborator: (none)
• Enrollment: 46
• Arm: 1
• Duration (Months): 33

Study Details

Study Description

Brief Summary

To determine the long term safety and tolerability of dasatinib exposure in subjects previously treated in CA180-002.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Dasatinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Long-Term Safety and Efficacy of Dasatinib (BMS-354825) in Chronic Myelogenous Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia in Subjects Who Experienced Clinical Benefit on Protocol CA180-002
• Study Start Date: Dec 1, 2005
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Dasatinib

Drug: Dasatinib; Tablets, Oral, The dosing ranges from 50mg to a total of 240mg daily with the following 3 schedules: 5 days on, 2 days off 6 days on, 1 day off Continuous daily dosing Once Daily (QD) or Twice Daily (BID) dosing, Subjects will be treated until progression of disease despite escalation/reductions of dose to the level deemed safe by available data, until intolerable/unacceptable toxicity or until subject withdrawal from the study or discontinuation of the study; Other Names: BMS-354825 Sprycel Src Kinase

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation. [From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.]

   AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled.

2. Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs. [From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.]

   Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy.

3. Number of Participants With Grade 3-4 Hematology Abnormalities [From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.]

   Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Platelets: Grade 3: 25.0 - <50.0*10^9/L, Grade 4: <25.0*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - <2.0*10^9/L, Grade 4: <1.0*10^9/L.

4. Number of Participants With Grade 3-4 Serum Chemistry Abnormalities [From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.]

   Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 * ULN (upper limit of normal), Grade 4: >20.0 * ULN; Calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; Bilirubin: Grade 3: >3-10 * ULN, Grade 4: >10 * ULN; Creatinine: Grade 3: >3.0-6.0 * ULN, Grade 4: >6.0 * ULN; Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-<0.8 or >2.46-6.6mEq/L, Grade 4: <0.6 or >6.6mEq/L.

5. Number of Participants With Dose Interruptions and Dose Reductions [From start of study to final assessment (up to 32.2 months).]

   Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times.

Secondary Outcome Measures

1. Number of Participants With Complete Hematologic Response (CHR) [Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   CHR should meet all of the following criteria: WBC <= Institutional ULN; ANC >= 1000/mm^3 ; Platelets < 450 000/mm^3 , no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood < 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment.

2. Median Number of Months of CHR (Kaplan Meier Method) [Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   CHR: WBC<=ULN (range: 9.29-12.5*10^3 c\uL); ANC >=1000/mm^3;Platelets <450000/mm^3,no blasts/promyelocytes in peripheral blood; <5% myelocytes+metamyelocytes in peripheral blood; basophils in peripheral blood <20% & no extramedullary involvement. Duration computed for chronic phase participants, measured in months from first day CHR criteria met, provided they are confirmed 4 weeks later, until progression of disease, treatment discontinuation due to progressive disease or death. Participants who neither discontinue due to progression, nor progress nor die censored on date of last assessment.

3. Number of Participants With Major Cytogenetic Response (MCyR) [Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   Cytogenetic responses are based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. MCyR is defined as number of participants with Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.

4. Median Number of Months of Major Cytogenetic Response (MCyR) [Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   MCyR: 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.The duration of MCyR was computed for chronic phase participants whose best response is either CCyR or PCyR. It was measured in months from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the date of progression or death. Participants who neither progress nor die are censored on the date of their last cytogenetic assessment.

5. Number of Participants With Best Cytogenetic Response [Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   Cytogenetic responses are based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR: 0% Ph+ cells in metaphase in bone marrow, PCyR: >0% to 35% Ph+ cells in metaphase in bone marrow, Minor CyR: >35% to 65% Ph+ cells in metaphase in bone marrow, Minimal CyR: >65% to 95% Ph+ cells in metaphase in bone marrow and No CyR: >95% to 100% Ph+ cells in metaphase in bone marrow.

6. Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method) [Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used.

7. Median Number of Months of Overall Survival (OS) (Kaplan Meier Method) [Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.]

   Overall survival was defined as the median number of months from baseline to death from any cause.

Eligibility Criteria

Criteria

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

This study enrolled participants with Philadelphia chromosome positive (Ph+)chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia (ALL) who had demonstrated hematologic resistance or intolerance to imatinib mesylate (Gleevec) and had experienced clinical benefit (in Investigator's opinion) on protocol CA180002.

Inclusion Criteria:

• Signed written informed consent

• Previous treatment with dasatinib on protocol CA180-002 and receiving clinical benefit in the opinion of the investigator

• Completed a minimum of 3 months on protocol CA180-002

• Eastern Cooperative Oncology Group (ECOG)performance status 0, 1, or 2 (See Appendix

• Prior history of Ph+ chronic, accelerated, or blast phase CML or Ph+ ALL

Exclusion Criteria:

• Women of childbearing potential(WOCBP)who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study

• WOCBP using a prohibited contraceptive method

• Women who are pregnant or breastfeeding

• Met the criteria as defined in protocol CA180-002 for discontinuation of therapy which includes:

• Withdrawal of informed consent (subject's decision to withdraw for any reason)

• Any clinical adverse event, laboratory abnormality or intercurrent illness which, in the opinion of the investigator, indicates that continued treatment with dasatinib is not in the best interest of the subject

• Imprisonment or the compulsory detention for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Medical History and Concurrent Diseases

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

• Uncontrolled angina within 3 months

• Diagnosed or suspected congenital long QT syndrome

• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)

• Prolonged corrected QT(QTc) interval on pre-entry electrocardiogram (> 450 msec)

• Uncontrolled hypertension

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

• History of significant bleeding disorder unrelated to CML, including:

1. Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)

2. Diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies)

Physical and Laboratory Test Findings

• Total bilirubin ≥ 1.5 mg/dl

• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 2 times the institutional upper limits of normal

• Serum creatinine ≥ 1.5 times the institutional upper limits of normal

Prohibited Therapies and/or Medications

• Patients currently taking drugs that are generally accepted to have a risk of causing

Torsades de Pointes including:

• quinidine, procainamide, disopyramide

• amiodarone, sotalol, ibutilide, dofetilide

• erythromycins, clarithromycin

• chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

• cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.

• Medications that inhibit platelet function and any non-steroidal anti-inflammatory drug) or anticoagulants are prohibited unless a previous exception on CA180-002 was granted by the medical monitor. Subjects taking anagrelide for thrombocytosis due to CML are eligible for this protocol

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00978731
• Other Study ID Numbers: CA180-039
• First Posted: Sep 17, 2009
• Last Update Posted: Apr 28, 2011
• Last Verified: Apr 1, 2011

• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Dasatinib

Study Results

Participant Flow

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Period Title: Overall Study
STARTED	22	15	5	4
COMPLETED	0	0	0	0
NOT COMPLETED	22	15	5	4

Baseline Characteristics

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry	Total
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Total of all reporting groups
Overall Participants	22	15	5	4	46
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	58	68	63	51	64
Age, Customized (participants) [Number]
< 65 years	12 54.5%	5 33.3%	3 60%	4 100%	24 52.2%
>= 65 years	10 45.5%	10 66.7%	2 40%	0 0%	22 47.8%
Sex: Female, Male (Count of Participants)
Female	11 50%	7 46.7%	4 80%	1 25%	23 50%
Male	11 50%	8 53.3%	1 20%	3 75%	23 50%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	18 81.8%	11 73.3%	3 60%	3 75%	35 76.1%
Black/African American	2 9.1%	3 20%	1 20%	0 0%	6 13%
Asian	0 0%	1 6.7%	0 0%	0 0%	1 2.2%
Other races	2 9.1%	0 0%	1 20%	1 25%	4 8.7%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (participants) [Number]
0 = fully active	18 81.8%	13 86.7%	3 60%	4 100%	38 82.6%
1 = restricted physically strenuous activity	4 18.2%	1 6.7%	2 40%	0 0%	7 15.2%
2 = ambulatory but unable to work	0 0%	0 0%	0 0%	0 0%	0 0%
3 = capable of only limited self care	0 0%	0 0%	0 0%	0 0%	0 0%
4 = completely disabled	0 0%	0 0%	0 0%	0 0%	0 0%
5 = dead	0 0%	0 0%	0 0%	0 0%	0 0%
Not reported	0 0%	1 6.7%	0 0%	0 0%	1 2.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Died, Experienced Other Serious Adverse Events (SAEs), Adverse Events (AEs) and AEs Leading to Study Drug Discontinuation.
Description	AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to AEs were recorded. These data differ from that in the Participant Flow section. This is because the data were collected on 2 different pages of the Case Report Form and were not reconciled.
Time Frame	From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	5	4
Deaths	3 13.6%	2 13.3%	1 20%	1 25%
SAEs	10 45.5%	9 60%	3 60%	3 75%
AEs	22 100%	15 100%	5 100%	4 100%
Discontinuation due to AEs	4 18.2%	3 20%	1 20%	0 0%

2. Primary Outcome

Title	Number of Participants Who Experienced Drug-related AEs and Drug-related SAEs.
Description	Drug-related AEs are those events with a relationship to the study therapy of certain; probable; or possible or missing. Drug-related SAEs are those events with any relationship to the study therapy.
Time Frame	From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	5	4
Drug-related AEs	14 63.6%	9 60%	3 60%	3 75%
Drug-related SAEs	4 18.2%	4 26.7%	1 20%	1 25%

3. Primary Outcome

Title	Number of Participants With Grade 3-4 Hematology Abnormalities
Description	Abnormalities were graded per the National Cancer Institute(NCI)Common Toxicity Criteria (CTC), v3.0(Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - <8.0g/dL, Grade 4: <6.5g/dL. Platelets: Grade 3: 25.0 - <50.0*10^9/L, Grade 4: <25.0*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - <1.0*10^9/L, Grade 4: <0.5*10^9/L.White Blood Cells (WBC) : Grade 3: 1.0 - <2.0*10^9/L, Grade 4: <1.0*10^9/L.
Time Frame	From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	5	4
WBC	2 9.1%	1 6.7%	0 0%	0 0%
ANC	3 13.6%	1 6.7%	0 0%	2 50%
Platelet Count	3 13.6%	1 6.7%	0 0%	1 25%
Hemoglobin	0 0%	1 6.7%	1 20%	1 25%

4. Secondary Outcome

Title	Number of Participants With Complete Hematologic Response (CHR)
Description	CHR should meet all of the following criteria: WBC <= Institutional ULN; ANC >= 1000/mm^3 ; Platelets < 450 000/mm^3 , no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; basophils in peripheral blood < 20% and no extramedullary involvement (including no hepatomegaly or splenomegaly). CHR can begin only 14 days after the start of treatment.
Time Frame	Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants. Data was not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	0	0
Number [participants]	16 72.7%	13 86.7%

5. Secondary Outcome

Title	Median Number of Months of CHR (Kaplan Meier Method)
Description	CHR: WBC<=ULN (range: 9.29-12.5*10^3 c\uL); ANC >=1000/mm^3;Platelets <450000/mm^3,no blasts/promyelocytes in peripheral blood; <5% myelocytes+metamyelocytes in peripheral blood; basophils in peripheral blood <20% & no extramedullary involvement. Duration computed for chronic phase participants, measured in months from first day CHR criteria met, provided they are confirmed 4 weeks later, until progression of disease, treatment discontinuation due to progressive disease or death. Participants who neither discontinue due to progression, nor progress nor die censored on date of last assessment.
Time Frame	Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants with CML (whether QD or BID dosing), who had CHR. Data were not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes.

Arm/Group Title	Participants With Chronic Myelogenous Leukemia (CML)
Arm/Group Description	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). QD dosing: TDD of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken QD. BID dosing: Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	29
Median (95% Confidence Interval) [months]	52.0

6. Secondary Outcome

Title	Number of Participants With Major Cytogenetic Response (MCyR)
Description	Cytogenetic responses are based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample. MCyR is defined as number of participants with Complete Cytogenetic Response (CCyR): 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.
Time Frame	Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants with evaluable sample sizes. Data was not analyzed and reported for the Accelerated Phase CML and Myeloid Blast Phase CML groups due to small sample sizes, which would lead to response rate estimates that are not stable.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	Participants With CML: BID Dosing at Study Entry
Arm/Group Description	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15
Number [participants]	13 59.1%	9 60%

7. Primary Outcome

Title	Number of Participants With Grade 3-4 Serum Chemistry Abnormalities
Description	Abnormalities were graded per the NCI (CTC), v3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Alanine aminotransferase (ALT): Grade 3: 5.0-20.0 * ULN (upper limit of normal), Grade 4: >20.0 * ULN; Calcium: Grade 3: 6.0-<7.0 or >12.5-13.5 mg/dL, Grade 4: <0.6->13.5 mg/dL; Bilirubin: Grade 3: >3-10 * ULN, Grade 4: >10 * ULN; Creatinine: Grade 3: >3.0-6.0 * ULN, Grade 4: >6.0 * ULN; Albumin: Grade 3: <2g/dL (Grade 4 not defined in NCI CTC); Magnesium: Grade 3: 0.6-<0.8 or >2.46-6.6mEq/L, Grade 4: <0.6 or >6.6mEq/L.
Time Frame	From start of study until up to 30 days after end of study participation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	5	4
Low Albumin	1 4.5%	0 0%	0 0%	0 0%
High ALT	1 4.5%	1 6.7%	0 0%	0 0%
High Total Bilirubin	0 0%	0 0%	0 0%	0 0%
Low Calcium	0 0%	0 0%	0 0%	0 0%
Low Magnesium	0 0%	0 0%	0 0%	0 0%
High Serum Creatinine	0 0%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Median Number of Months of Major Cytogenetic Response (MCyR)
Description	MCyR: 0% Ph+ cells in metaphase in bone marrow or Partial Cytogenetic Response (PCyR): >0% to 35% Ph+ cells in metaphase in bone marrow.The duration of MCyR was computed for chronic phase participants whose best response is either CCyR or PCyR. It was measured in months from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the date of progression or death. Participants who neither progress nor die are censored on the date of their last cytogenetic assessment.
Time Frame	Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants with CML (whether QD or BID dosing), who had MCyR (13 participants had MCyR in QD group and 9 in BID group). Data were not analyzed and reported for the other two groups (Accelerated Phase CML and Myeloid Blast Phase CML) due to small sample sizes.

Arm/Group Title	Participants With Chronic Myelogenous Leukemia (CML)
Arm/Group Description	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). QD dosing: TDD of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken QD. BID dosing: Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22
Median (95% Confidence Interval) [months]	50.1

9. Primary Outcome

Title	Number of Participants With Dose Interruptions and Dose Reductions
Description	Dose interruptions and reductions were allowed, in order to optimize individual participant's hematologic, cytogenetic, and molecular response while maintaining and evaluating safety and tolerability of long-term exposure to dasatinib. A dose reduction is defined as the administration of a dose at a lower level compared to previous dose and such that reduced dose, or a lower dose, is given at least 4 consecutive times. In determining the reductions, dose level would be compared to the previous non-null dose. Dose interruption is defined as a complete omission of dosing for 4 consecutive times.
Time Frame	From start of study to final assessment (up to 32.2 months).

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	CML: BID Dosing at Study Entry	Accelerated Phase CML: BID Dosing at Study Entry	Myeloid Blast Phase CML: BID Dosing at Study Entry
Arm/Group Description	Participants with Chronic Myelogenous Leukemia (CML)were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with accelerated phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants with myeloid blast phase CML were continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15	5	4
Dose interruptions	7 31.8%	9 60%	2 40%	2 50%
Dose reductions	8 36.4%	4 26.7%	2 40%	1 25%

10. Secondary Outcome

Title	Number of Participants With Best Cytogenetic Response
Description	Cytogenetic responses are based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample. CCyR: 0% Ph+ cells in metaphase in bone marrow, PCyR: >0% to 35% Ph+ cells in metaphase in bone marrow, Minor CyR: >35% to 65% Ph+ cells in metaphase in bone marrow, Minimal CyR: >65% to 95% Ph+ cells in metaphase in bone marrow and No CyR: >95% to 100% Ph+ cells in metaphase in bone marrow.
Time Frame	Pre-treatment to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants with evaluable sample sizes. Data was not analyzed and reported for the Accelerated Phase CML and Myeloid Blast Phase CML groups due to small sample sizes, which would lead to response rate estimates that are not stable.

Arm/Group Title	Chronic Myelogenous Leukemia (CML): QD Dosing at Study Entry	Participants With CML: BID Dosing at Study Entry
Arm/Group Description	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol CA180002 (NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg dasatinib. Participants were dosed on 1 of 3 schedules (5 days on, 2 days off; 6 days on, 1 day off or continuous daily dosing) and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
Measure Participants	22	15
Complete (0%)	10 45.5%	7 46.7%
Partial (1-35%)	3 13.6%	2 13.3%
Minor (36-65%)	0 0%	1 6.7%
Minimal (66-95%)	3 13.6%	1 6.7%
No response	4 18.2%	3 20%
Unable to determine	2 9.1%	1 6.7%

11. Secondary Outcome

Title	Median Number of Months of Progression-free Survival (PFS) (Kaplan Meier Method)
Description	Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used.
Time Frame	Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	All participants treated in each arm of the study were included.
Measure Participants	46
Median (95% Confidence Interval) [months]	32.0

12. Secondary Outcome

Title	Median Number of Months of Overall Survival (OS) (Kaplan Meier Method)
Description	Overall survival was defined as the median number of months from baseline to death from any cause.
Time Frame	Baseline to study discontinuation. Median duration of exposure (on-study time) was 23.4 months.

Outcome Measure Data

Analysis Population Description

All treated participants.

Arm/Group Title	All Participants
Arm/Group Description	All participants treated in each arm of the study were included.
Measure Participants	46
Median (95% Confidence Interval) [months]	NA

Adverse Events

Adverse Event Reporting Description	The SAEs listed here differ from those present in the Outcome Measures. This is because the Outcome Measures present on-treatment SAEs and this section presents all SAEs. In addition, the AEs presented here differ from those in the Outcome Measures. This is because the AEs presented here do not include SAEs.
Arm/Group Title	Participants With Accelerated Phase CML		Participants With Chronic Myelogenous Leukemia(CML);QD Dosing		Participants With CML; BID Dosing		Participants With Myeloid Blast Phase CML
Arm/Group Description	Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg ). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.		Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A total daily dose (TDD) of 50 mg, 75 mg, 105 mg, 140 mg or 180 mg dasatinib was taken once daily (QD). Participants were dosed on 1 of 3 schedules: 5 days, on 2 days off; 6 days on, 1 day off; or continuous daily dosing. Participants were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to twice daily (BID) dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.		Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). Treatment was received BID, with a TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg. Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.		Participants continued on the last dose and schedule of dasatinib that was received within the previous protocol (CA180002; NCT00064233). A TDD of 50 mg, 75 mg, 105 mg, 120 mg, 140 mg or 180 mg dasatinib was taken QD or split into 2 doses and taken BID (TDD of 50 mg, 70 mg, 100 mg, 140 mg, 180 mg or 240 mg ). Participants were dosed on 1 of 3 schedules: 5 days on, 2 days off; 6 days on, 1 day off; or continuous daily dosing and were permitted to escalate or reduce by 1 dose level at a time, switch from QD dosing to BID dosing and vice versa provided they did not exceed a change of 1 dose level from the TDD. The weekly schedule was also permitted to be increased or decreased 1 level at a time.
All Cause Mortality
	Participants With Accelerated Phase CML		Participants With Chronic Myelogenous Leukemia(CML);QD Dosing		Participants With CML; BID Dosing		Participants With Myeloid Blast Phase CML
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Participants With Accelerated Phase CML		Participants With Chronic Myelogenous Leukemia(CML);QD Dosing		Participants With CML; BID Dosing		Participants With Myeloid Blast Phase CML
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/5 (60%)		10/22 (45.5%)		9/15 (60%)		3/4 (75%)
Blood and lymphatic system disorders
ANAEMIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Cardiac disorders
ARRHYTHMIA	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
MYOCARDIAL ISCHAEMIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
PERICARDIAL EFFUSION	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
CARDIO-RESPIRATORY ARREST	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
ACUTE MYOCARDIAL INFARCTION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Gastrointestinal disorders
DIARRHOEA	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
HAEMORRHOIDS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
OESOPHAGITIS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
ABDOMINAL HERNIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
GASTROINTESTINAL HAEMORRHAGE	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
General disorders
DEATH	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
HERNIA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
PYREXIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Infections and infestations
PNEUMONIA	0/5 (0%)		3/22 (13.6%)		2/15 (13.3%)		1/4 (25%)
UROSEPSIS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
MENINGITIS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
APPENDICITIS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
ARTHRITIS BACTERIAL	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
CATHETER SITE CELLULITIS	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
STAPHYLOCOCCAL INFECTION	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
HERPES ZOSTER DISSEMINATED	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
JOINT INJURY	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
TRANSFUSION-RELATED ACUTE LUNG INJURY	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Metabolism and nutrition disorders
ANOREXIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
DEHYDRATION	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
HYPONATRAEMIA	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
METASTASIS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
BASAL CELL CARCINOMA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
LUNG NEOPLASM MALIGNANT	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
BLAST CELL PROLIFERATION	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
CHRONIC MYELOID LEUKAEMIA	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
TRANSITIONAL CELL CARCINOMA	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Nervous system disorders
HEADACHE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
CEREBRAL HAEMORRHAGE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
HAEMORRHAGE INTRACRANIAL	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Psychiatric disorders
MENTAL STATUS CHANGES	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Renal and urinary disorders
RENAL FAILURE ACUTE	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
DYSPNOEA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
LUNG DISORDER	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
PLEURAL EFFUSION	1/5 (20%)		1/22 (4.5%)		2/15 (13.3%)		0/4 (0%)
SLEEP APNOEA SYNDROME	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Vascular disorders
PERIPHERAL VASCULAR DISORDER	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Participants With Accelerated Phase CML		Participants With Chronic Myelogenous Leukemia(CML);QD Dosing		Participants With CML; BID Dosing		Participants With Myeloid Blast Phase CML
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/5 (100%)		21/22 (95.5%)		15/15 (100%)		4/4 (100%)
Blood and lymphatic system disorders
ANAEMIA	0/5 (0%)		2/22 (9.1%)		2/15 (13.3%)		0/4 (0%)
SPLENOMEGALY	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Cardiac disorders
TACHYCARDIA	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
CARDIAC DISORDER	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
DILATATION ATRIAL	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
PERICARDIAL EFFUSION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
DIASTOLIC DYSFUNCTION	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
MYOCARDIAL INFARCTION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
CORONARY ARTERY DISEASE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
VENTRICULAR TACHYCARDIA	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
RIGHT VENTRICULAR DYSFUNCTION	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Ear and labyrinth disorders
VERTIGO	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Eye disorders
EYE PRURITUS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
VISION BLURRED	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
OCULAR HYPERAEMIA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
Gastrointestinal disorders
NAUSEA	1/5 (20%)		1/22 (4.5%)		4/15 (26.7%)		0/4 (0%)
VOMITING	0/5 (0%)		4/22 (18.2%)		3/15 (20%)		1/4 (25%)
DIARRHOEA	0/5 (0%)		4/22 (18.2%)		3/15 (20%)		1/4 (25%)
DRY MOUTH	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
ORAL PAIN	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
FLATULENCE	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
GINGIVITIS	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
STOMATITIS	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
CONSTIPATION	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
DIVERTICULUM	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
ABDOMINAL PAIN	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
SWOLLEN TONGUE	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
RECTAL HAEMORRHAGE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		1/4 (25%)
STOMACH DISCOMFORT	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
SALIVARY GLAND CALCULUS	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
GASTROINTESTINAL HAEMORRHAGE	0/5 (0%)		3/22 (13.6%)		0/15 (0%)		0/4 (0%)
General disorders
MASS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
POLYP	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
CHILLS	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
FATIGUE	1/5 (20%)		10/22 (45.5%)		3/15 (20%)		2/4 (50%)
PYREXIA	1/5 (20%)		3/22 (13.6%)		2/15 (13.3%)		1/4 (25%)
ASTHENIA	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
CALCINOSIS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
CHEST PAIN	1/5 (20%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
CHEST DISCOMFORT	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
OEDEMA PERIPHERAL	1/5 (20%)		4/22 (18.2%)		1/15 (6.7%)		2/4 (50%)
INFLUENZA LIKE ILLNESS	1/5 (20%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Infections and infestations
CYSTITIS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
MASTITIS	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
PNEUMONIA	0/5 (0%)		6/22 (27.3%)		0/15 (0%)		0/4 (0%)
SINUSITIS	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		1/4 (25%)
BRONCHITIS	0/5 (0%)		2/22 (9.1%)		2/15 (13.3%)		0/4 (0%)
HEPATITIS B	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
ORAL HERPES	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
FOLLICULITIS	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
LYME DISEASE	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
LOBAR PNEUMONIA	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
NASOPHARYNGITIS	0/5 (0%)		0/22 (0%)		2/15 (13.3%)		1/4 (25%)
VIRAL INFECTION	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
URINARY TRACT INFECTION	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		1/4 (25%)
RESPIRATORY TRACT INFECTION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
UPPER RESPIRATORY TRACT INFECTION	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		1/4 (25%)
URINARY TRACT INFECTION ENTEROCOCCAL	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Injury, poisoning and procedural complications
CONTUSION	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		1/4 (25%)
JOINT INJURY	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Investigations
CARDIAC MURMUR	0/5 (0%)		2/22 (9.1%)		2/15 (13.3%)		0/4 (0%)
BLOOD CREATININE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
WEIGHT DECREASED	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
CHEST X-RAY ABNORMAL	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
BREATH SOUNDS ABNORMAL	0/5 (0%)		3/22 (13.6%)		1/15 (6.7%)		0/4 (0%)
ALANINE AMINOTRANSFERASE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
BLOOD CHLORIDE INCREASED	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
BLOOD URIC ACID INCREASED	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Metabolism and nutrition disorders
ANOREXIA	1/5 (20%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
DEHYDRATION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
MYALGIA	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
BACK PAIN	0/5 (0%)		3/22 (13.6%)		0/15 (0%)		0/4 (0%)
BONE PAIN	1/5 (20%)		2/22 (9.1%)		0/15 (0%)		1/4 (25%)
ARTHRALGIA	1/5 (20%)		3/22 (13.6%)		0/15 (0%)		1/4 (25%)
SPONDYLITIS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
OSTEOPOROSIS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
MUSCLE SPASMS	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
PAIN IN EXTREMITY	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
MUSCULOSKELETAL PAIN	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		1/4 (25%)
Nervous system disorders
HEADACHE	1/5 (20%)		1/22 (4.5%)		4/15 (26.7%)		0/4 (0%)
DIZZINESS	0/5 (0%)		2/22 (9.1%)		2/15 (13.3%)		0/4 (0%)
HYPOAESTHESIA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
Renal and urinary disorders
NOCTURIA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
HAEMATURIA	1/5 (20%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
POLLAKIURIA	1/5 (20%)		1/22 (4.5%)		0/15 (0%)		0/4 (0%)
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
BENIGN PROSTATIC HYPERPLASIA	0/5 (0%)		1/22 (4.5%)		0/15 (0%)		1/4 (25%)
Respiratory, thoracic and mediastinal disorders
COUGH	1/5 (20%)		5/22 (22.7%)		1/15 (6.7%)		0/4 (0%)
ASTHMA	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
HYPOXIA	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
DYSPNOEA	1/5 (20%)		6/22 (27.3%)		3/15 (20%)		0/4 (0%)
EPISTAXIS	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
ATELECTASIS	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
BRONCHOSPASM	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
PLEURITIC PAIN	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
PLEURAL EFFUSION	2/5 (40%)		6/22 (27.3%)		5/15 (33.3%)		1/4 (25%)
PULMONARY OEDEMA	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
SINUS CONGESTION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
RHINITIS ALLERGIC	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
OROPHARYNGEAL PAIN	0/5 (0%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
DYSPNOEA EXERTIONAL	0/5 (0%)		4/22 (18.2%)		2/15 (13.3%)		0/4 (0%)
PULMONARY HYPERTENSION	2/5 (40%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
PARANASAL SINUS HYPERSECRETION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
Skin and subcutaneous tissue disorders
ACNE	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
RASH	1/5 (20%)		2/22 (9.1%)		1/15 (6.7%)		0/4 (0%)
ECCHYMOSIS	0/5 (0%)		1/22 (4.5%)		2/15 (13.3%)		0/4 (0%)
SKIN ULCER	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
SKIN LESION	0/5 (0%)		2/22 (9.1%)		0/15 (0%)		0/4 (0%)
NIGHT SWEATS	1/5 (20%)		1/22 (4.5%)		0/15 (0%)		1/4 (25%)
HYPERHIDROSIS	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
Vascular disorders
PALLOR	1/5 (20%)		0/22 (0%)		0/15 (0%)		0/4 (0%)
HAEMATOMA	0/5 (0%)		0/22 (0%)		0/15 (0%)		1/4 (25%)
HYPERTENSION	0/5 (0%)		1/22 (4.5%)		1/15 (6.7%)		0/4 (0%)
VASCULAR CALCIFICATION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)
INTERMITTENT CLAUDICATION	0/5 (0%)		0/22 (0%)		1/15 (6.7%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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