Rollover Study of BMS-354825 in Patients With CML and Ph+ALL

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01030718
• Collaborator: (none)
• Enrollment: 54
• Arms: 3
• Duration (Months): 41

Study Details

Study Description

Brief Summary

To assess the safety of dasatinib (BMS-354825) in subjects with Imatinib resistant or intolerant chronic myelogenous leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) who are resistant or intolerant to treatment and will continue study drug after completing the previous Phase I/II study (CA180031/NCT00337454)

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia	Drug: dasatinib	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Document the Long-Term Safety and Efficacy of BMS-354825 in Subjects With Imatinib Resistant or Intolerant Chronic Myelogenous Leukemia and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Previous Treatment and Have Completed the Previous Phase I/II Protocol (CA180-031/NCT00337454)
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: dasatinib (CML-CP) CML - Chronic Phase	Drug: dasatinib; Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID; Other Names: Sprycel BMS-354825
Experimental: dasatinib (CML-AP/BP) CML - Accelerated Phase and Blast Phase	Drug: dasatinib; Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID; Other Names: Sprycel BMS-354825
Experimental: dasatinib (Ph+ ALL) Ph+ Acute Lymphoblastic Leukemia	Drug: dasatinib; Tablet, Oral, (50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID; Other Names: Sprycel BMS-354825

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation [baseline; every 4 weeks (if on study < 6 months, including CA180-031(NCT00337454); every 12 weeks (if on study >=6 months and <=2 years); every 24 weeks (if on study >2 years); at discontinuation]

   AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.

Secondary Outcome Measures

1. Participants With Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response [At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Philadelphia positive [Ph+] Cells in Metaphase in BM).

2. Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).

3. Participants With Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL): Percentage of Participants With Cytogenetic Response [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).

4. Participants With CML-CP: Time to Complete Cytogenetic Response (CCyR) [At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454),]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.

5. Participants With CML-AP/BP and Ph+ ALL: Time to Complete Cytogenetic Response (CCyR) [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.

6. Participants With CML-CP: Duration of Complete Cytogenetic Response (CCyR) [At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of progressed disease (PD) or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.

7. Participants With CML-AP/BP and Ph+ALL: Duration of Complete Cytogenetic Response (CCyR) [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

   Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of PD or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.

8. Participants With CML-CP: Time to Major Cytogenetic Response (MCyR) [At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)]

   Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).

9. Participants With CML-AP/BP and Ph+ALL: Time to Major Cytogenetic Response (MCyR) [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

   Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).

10. Participants With CML-CP: Duration of Major Cytogenetic Response (MCyR) [At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)]

    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.

11. Participants With CML-AP/BP and Ph+ ALL: Duration of Major Cytogenetic Response (MCyR) [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter]

    Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.

12. Participants With CML-CP: Percentage of Participants With Complete Hematologic Response (CHR) [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454), every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    CHR=all of the following criteria: white blood cell count (WBC) ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement.

13. Participants With CML-AP/BP: Percentage of Participants With Hematologic Response [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=WBC <ULN; absolute neutrophil count (ANC) >1,000/mm3; platelets >100,000/mm3; no blasts or promyelocytes in peripheral blood; BM blasts ≤5%; <5% myelocytes + metamyelocytes in peripheral blood; <20% basophils in peripheral blood; no extramedullary involvement. NEL=(see Outcome Measure 15, below). Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).

14. Participants With Ph+ ALL: Percentage of Participants With Hematologic Response [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=(see Outcome Measure 14, above). NEL=WBC ≤ULN; BM blasts ≤5%; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; <20% peripheral blood basophils; no extramedullary involvement; and at least 1 of the following: ANC ≥500/mm3 and <2000/mm3 or platelets ≥20,000/mm3 and <100,000/mm3. Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).

15. Time to Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    CHR=all of the following criteria: WBC ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement. Time to CHR=time from first dose of dasatinib until the first day criteria for CHR are met provided they are confirmed 28 days later and was computed only for chronic phase CML subjects whose best response is CHR. Subjects who neither progressed nor died were censored at date of last hematologic assessment.

16. Duration of Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    Duration of CHR was computed only for chronic phase CML subjects whose best response is CHR. It was measured from the first day complete hematologic response criteria are met provided they are confirmed 28 days later until the date treatment is discontinued due to PD or death. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

17. Time to Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Time to major hematologic response (MaHR)=time from first dose of dasatinib until the first day the measurement criteria for MaHR and is computed only for advanced diseases subjects whose best response is a major hematologic response. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

18. Duration of Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    Major Hematologic Response (MaHR)=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.

19. Time to Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Time to OHR = time from first dose of dasatinib until the first day measurement criteria are first met for hematologic response provided they were confirmed 28 days later. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.

20. Duration of Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL [baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation]

    The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.

21. Participants With Detectable Mutations of RNA (mRNA) of BCR-ABL at Baseline and at Best Achievement [At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter, and at discontinuation]

    Detectable BCR-ABL transcripts (b3a2, b2a2 or minor) >=2.0 log copy/micrograms RNA, as measured by real-time quantitative PCR (RQ-PCR) at baseline and best achievement post-dose.

22. Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS) [At baseline and discontinuation--the study period was extended until the launch of dasatinib in Japan, January 2009.]

    Point mutations of BCR-ABL detected or undetected in the Quantitative real-time PCR polymerase chain reaction (RQ-PCR) products

23. Collection of Blood Samples for Pharmacokinetic Analysis of Dasatinib Twice Daily (BID) That Will Contribute to Population Pharmacokinetic Modeling [At any visit of later than Day 7, draw sample(s) at pretreatment trough (within 1 hour prior to dosing) or between 3 hours following treatment and prior to the next dose]

    Blood samples for pharmacokinetic analysis of Dasatinib BID that will contribute to population pharmacokinetic modeling were collected.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who were eligible and completed the previous Phase I and II study (CA180031/NCT00337454) and for whom the principal investigator has deemed that continuation of study drug is in the best interest of the subject

Exclusion Criteria:

• Women who are pregnant or breastfeeding

• Subjects who are eligible and willing to undergo transplantation at pre-study

• Non-hematologic intolerance to Dasatinib (BMS-354825) in the previous Phase I and II study (CA180031/NCT00337454)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT01030718
• Other Study ID Numbers: CA180-036
• First Posted: Dec 11, 2009
• Last Update Posted: Dec 14, 2010
• Last Verified: Nov 1, 2010

• Additional relevant MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Dasatinib

Study Results

Participant Flow

Recruitment Details	CA180-031 = NCT00337454; CA180-036 = NCT01030718
Pre-assignment Detail	55 participants were randomized to study CA180-031; 1 participant with chronic myelogenous leukemia-chronic phase (CML-CP) was withdrawn prior to dosing due to thrombocytopenia. 54 subjects were treated; 44 subjects finished the study period of CA180-031 and transferred CA180-036. Analyses were done on the population enrolled into CA180-031 study.

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Philadelphia chromosome positive (Ph+) ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Period Title: Studies CA180-031 and -036 Combined
STARTED	30	11	13
COMPLETED	26	2	1
NOT COMPLETED	4	9	12
Period Title: Studies CA180-031 and -036 Combined
STARTED	29	9	6
COMPLETED	26	2	1
NOT COMPLETED	3	7	5

Baseline Characteristics

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)	Total
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Total of all reporting groups
Overall Participants	30	11	13	54
Age, Customized (participants) [Number]
<65 years	26 86.7%	8 72.7%	10 76.9%	44 81.5%
>=65 years	4 13.3%	3 27.3%	3 23.1%	10 18.5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	51.5	57.0	64.0	55.5
Sex: Female, Male (Count of Participants)
Female	9 30%	4 36.4%	6 46.2%	19 35.2%
Male	21 70%	7 63.6%	7 53.8%	35 64.8%
Region of Enrollment (participants) [Number]
Japan	30 100%	11 100%	13 100%	54 100%
Eastern Oncology Cooperative Group Performance Status (participants) [Number]
Status = 0	27 90%	6 54.5%	9 69.2%	42 77.8%
Status = 1	3 10%	5 45.5%	4 30.8%	12 22.2%
Status = 2	0 0%	0 0%	0 0%	0 0%
Status = 3	0 0%	0 0%	0 0%	0 0%
Status = 4	0 0%	0 0%	0 0%	0 0%
Status = 5	0 0%	0 0%	0 0%	0 0%
Imatinib Status (participants) [Number]
Resistant	18 60%	8 72.7%	9 69.2%	35 64.8%
Intolerant	12 40%	3 27.3%	4 30.8%	19 35.2%
Body Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	64.05	58.00	53.20	60.55
Height (cm) [Median (Full Range) ]
Median (Full Range) [cm]	163.65	161.00	164.50	163.25

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, and Discontinuation
Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	baseline; every 4 weeks (if on study < 6 months, including CA180-031(NCT00337454); every 12 weeks (if on study >=6 months and <=2 years); every 24 weeks (if on study >2 years); at discontinuation

Outcome Measure Data

Analysis Population Description

All treated participants. Number of deaths represents all reported deaths, including after the study end. For AEs leading to discontinuation: 4 in CML-CP=1 insufficient effect (IE) +3 AEs in Participant Flow (PF); 7 in CML-AP/BP= 1 death + 5 AEs + 1 IE in PF; 4 in Ph+ALL=3 IE + 1AE in PF.

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	30	11	13
AEs (symptoms/signs and laboratory abnormalities)	30 100%	11 100%	13 100%
SAEs (symptoms/signs and laboratory abnormalities)	13 43.3%	9 81.8%	11 84.6%
Deaths	1 3.3%	2 18.2%	3 23.1%
AEs that led to discontinuation	4 13.3%	7 63.6%	4 30.8%

2. Secondary Outcome

Title	Participants With Chronic Phase CML (CML-CP): Percentage of Participants With Cytogenetic Response
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Philadelphia positive [Ph+] Cells in Metaphase in BM).
Time Frame	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)

Outcome Measure Data

Analysis Population Description

Treated CML-CP participants

Arm/Group Title	CML - Chronic Phase (CML-CP) Total	CML - Chronic Phase (CML-CP) - Imatinib Resistant	CML - Chronic Phase (CML-CP) - Imatinib Intolerant
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant CML-CP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	30	11	12
Major cytogenetic response (MCyR)	77 256.7%	61 554.5%	100 769.2%
Complete cytogenetic response (CCyR)	63 210%	44 400%	92 707.7%

3. Secondary Outcome

Title	Participants With CML-Accelerated or Blast Phase (AP/BP): Percentage of Participants With Cytogenetic Response
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Treated CML-AP/BP participants

Arm/Group Title	CML-AP/BP - Total Cohort	CML-AP/BP - Imatinib Resistant	CML-AP/BP - Imatinib Intolerant
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	11	8	3
Major cytogenetic response (MCyR)	27 90%	38 345.5%	0 0%
Complete cytogenetic response (CCyR)	18 60%	25 227.3%	0 0%

4. Secondary Outcome

Title	Participants With Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL): Percentage of Participants With Cytogenetic Response
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. The criteria for cytogenetic responses are as follows. Best CyR is defined as the best response obtained at any time during the study. Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM).
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Treated Ph+ ALL participants

Arm/Group Title	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Total Cohort	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Resistant	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Intolerant
Arm/Group Description	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	13	9	4
Major cytogenetic response (MCyR)	54 180%	33 300%	100 769.2%
Complete cytogenetic response (CCyR)	46 153.3%	22 200%	100 769.2%

5. Secondary Outcome

Title	Participants With CML-CP: Time to Complete Cytogenetic Response (CCyR)
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.
Time Frame	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454),

Outcome Measure Data

Analysis Population Description

Participants achieving CCyR

Arm/Group Title	CML - Chronic Phase (CML-CP)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	19
Median (Full Range) [Days]	169

6. Secondary Outcome

Title	Participants With CML-AP/BP and Ph+ ALL: Time to Complete Cytogenetic Response (CCyR)
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Time to complete CCyR is defined as the time from first dose of dasatinib until measurement criteria are first met for CCyR, and is computed only for subjects whose best response is CCyR.
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Participants achieving CCyR

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	2	6
Median (Full Range) [Days]	215	82

7. Secondary Outcome

Title	Participants With CML-CP: Duration of Complete Cytogenetic Response (CCyR)
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of progressed disease (PD) or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.
Time Frame	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)

Outcome Measure Data

Analysis Population Description

Participants achieving CCyR. Median duration of CCyR was not yet reached in the CML-CP group.

Arm/Group Title	CML - Chronic Phase (CML-CP)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0

8. Secondary Outcome

Title	Participants With CML-AP/BP and Ph+ALL: Duration of Complete Cytogenetic Response (CCyR)
Description	Cytogenetic responses (CyR) are based on the percentage of Ph+ metaphases among at least 20 metaphase cells in each bone marrow (BM) sample. Complete Cytogenetic Response (CCyR) = 0 Ph+ Cells in Metaphase in BM. Duration of CCyR was measured from the time measurement criteria are first met for CCyR until the first date of PD or death. Subjects who neither relapsed nor died will be censored on the date of their last assessment.
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Participants achieving CCyR. Median duration of CCyR was not yet reached in the CML-AP/BP group.

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0	6
Median (Full Range) [Days]	96.5

9. Secondary Outcome

Title	Participants With CML-CP: Time to Major Cytogenetic Response (MCyR)
Description	Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).
Time Frame	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)

Outcome Measure Data

Analysis Population Description

Time to MCyR was computed only for participants whose best response was CCyR or PCyR.

Arm/Group Title	CML - Chronic Phase (CML-CP)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	23
Median (Full Range) [Days]	169

10. Secondary Outcome

Title	Participants With CML-AP/BP and Ph+ALL: Time to Major Cytogenetic Response (MCyR)
Description	Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Time to MCyR was defined as the time from first dose of dasatinib until measurement criteria were first met for CCyR or PCyR (whichever status is recorded first).
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Time to MCyR was computed only for participants whose best response was CCyR or PCyR.

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	3	7
Median (Full Range) [Days]	85	85

11. Secondary Outcome

Title	Participants With CML-CP: Duration of Major Cytogenetic Response (MCyR)
Description	Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.
Time Frame	At baseline, every 24 weeks thereafter (including study CA180031/NCT00337454)

Outcome Measure Data

Analysis Population Description

Duration of MCyR was computed for subjects whose best response was either CCyR or PCyR. Median duration of MCyR was not yet reached in the CML-CP arm.

Arm/Group Title	CML - Chronic Phase (CML-CP)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0

12. Secondary Outcome

Title	Participants With CML-AP/BP and Ph+ ALL: Duration of Major Cytogenetic Response (MCyR)
Description	Major Cytogenetic Response (MCyR) = Complete Cytogenetic Response (CCyR; 0 Ph+ Cells in Metaphase in BM), plus Partial Cytogenetic Response (PCyR; 1 - 35 Ph+ Cells in Metaphase in BM). Duration of MCyR was measured from the time measurement criteria are first met for CCyR or PCyR (whichever status is recorded first) until the first date of progressive disease (PD) or death. Subjects who neither relapsed nor died were censored on the date of their last assessment.
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter

Outcome Measure Data

Analysis Population Description

Duration of MCyR was computed for subjects whose best response was either CCyR or PCyR. Median duration of MCyR was not yet reached in the CML-AP/BP arm.

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0	7
Median (Full Range) [Days]	85

13. Secondary Outcome

Title	Participants With CML-CP: Percentage of Participants With Complete Hematologic Response (CHR)
Description	CHR=all of the following criteria: white blood cell count (WBC) ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454), every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Treated CML-CP participants

Arm/Group Title	CML - Chronic Phase (CML-CP) Total	CML - Chronic Phase (CML-CP) - Imatinib Resistant	CML - Chronic Phase (CML-CP) - Imatinib Intolerant
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant CML-CP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib intolerant CML-CP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	30	18	12
Number (95% Confidence Interval) [Percentage of Participants]	93 310%	89 809.1%	100 769.2%

14. Secondary Outcome

Title	Participants With CML-AP/BP: Percentage of Participants With Hematologic Response
Description	Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=WBC <ULN; absolute neutrophil count (ANC) >1,000/mm3; platelets >100,000/mm3; no blasts or promyelocytes in peripheral blood; BM blasts ≤5%; <5% myelocytes + metamyelocytes in peripheral blood; <20% basophils in peripheral blood; no extramedullary involvement. NEL=(see Outcome Measure 15, below). Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Treated CML-AP/BP participants

Arm/Group Title	CML-AP/BP - Total Cohort	CML-AP/BP - Imatinib Resistant	CML-AP/BP - Imatinib Intolerant
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	11	8	3
Overall hematologic response (OHR)	73 243.3%	75 681.8%	67 515.4%
Major hematologic response (MaHR)	73 243.3%	75 681.8%	67 515.4%
Complete hematologic response (CHR)	55 183.3%	75 681.8%	0 0%

15. Secondary Outcome

Title	Participants With Ph+ ALL: Percentage of Participants With Hematologic Response
Description	Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL). CHR=(see Outcome Measure 14, above). NEL=WBC ≤ULN; BM blasts ≤5%; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; <20% peripheral blood basophils; no extramedullary involvement; and at least 1 of the following: ANC ≥500/mm3 and <2000/mm3 or platelets ≥20,000/mm3 and <100,000/mm3. Overall hematologic response (OHR)=best response of CHR, NEL or return to chronic phase (RTC).
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Treated Ph+ ALL participants

Arm/Group Title	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Total Cohort	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Resistant	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) - Intolerant
Arm/Group Description	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031, allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	13	9	4
Overall hematologic response (OHR)	69 230%	56 509.1%	100 769.2%
Major hematologic response (MaHR)	46 153.3%	33 300%	75.5 580.8%
Complete hematologic response (CHR)	15 50%	0 0%	50 384.6%

16. Secondary Outcome

Title	Time to Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL
Description	CHR=all of the following criteria: WBC ≤institutional upper limit of normal(ULN); platelets <450,000/mm³; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils <20%; no extramedullary involvement. Time to CHR=time from first dose of dasatinib until the first day criteria for CHR are met provided they are confirmed 28 days later and was computed only for chronic phase CML subjects whose best response is CHR. Subjects who neither progressed nor died were censored at date of last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Participants achieving CHR

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	29	6	2
Median (Full Range) [Days]	12.5	89	98.5

17. Secondary Outcome

Title	Duration of Complete Hematologic Response (CHR) in Chronic Phase CML, Accelerated or Blast Phase CML, and Ph+ALL
Description	Duration of CHR was computed only for chronic phase CML subjects whose best response is CHR. It was measured from the first day complete hematologic response criteria are met provided they are confirmed 28 days later until the date treatment is discontinued due to PD or death. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Participants achieving CHR. Duration of CHR in the CML AP/BP arm has not yet been reached.

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	29	0	2
Median (Full Range) [Days]	1160	373

18. Secondary Outcome

Title	Time to Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL
Description	Major Hematologic Response=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Time to major hematologic response (MaHR)=time from first dose of dasatinib until the first day the measurement criteria for MaHR and is computed only for advanced diseases subjects whose best response is a major hematologic response. Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Participants achieving MaHR

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	8	6
Median (Full Range) [Days]	45.5	59

19. Secondary Outcome

Title	Duration of Major Hematologic Response (MaHR) in Accelerated or Blast Phase CML, and Ph+ALL
Description	Major Hematologic Response (MaHR)=Complete Hematologic Response (CHR) or No Evidence of Leukemia (NEL; see Outcome Measures 14 and 15 for full definitions). Subjects who neither progressed nor died were censored on the date of their last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Duration of MaHR was computed only for advanced diseases subjects whose best response is a MaHR and was measured from the first day MaHR criteria are met, provided they were confirmed 28 days later until the date of PD or death. Median Duration of MaHR was not yet reached in the CML-AP/BP arm.

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0	6
Median (Full Range) [Days]	102.5

20. Secondary Outcome

Title	Time to Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL
Description	The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Time to OHR = time from first dose of dasatinib until the first day measurement criteria are first met for hematologic response provided they were confirmed 28 days later. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

OHR was computed only for subjects whose best response is CHR or MaHR or Minor HR (MiHR).

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	8	9
Median (Full Range) [Days]	38.5	13

21. Secondary Outcome

Title	Duration of Overall Hematologic Response (OHR) in Accelerated or Blast Phase CML, and Ph+ALL
Description	The overall hematologic response (OHR) rate is defined as the proportion of all treated subjects with a best response of major or minor hematologic response. Subjects who neither progressed nor died were censored on the date of last hematologic assessment.
Time Frame	baseline; every 4 weeks < 6 months on study (including study CA180031/NCT00337454); every 12 weeks >=6 months and <=2 years; every 24 weeks >2 years; at discontinuation

Outcome Measure Data

Analysis Population Description

Duration of OHR was computed only for participants whose best response was CHR or a MaHR or MiHR & was measured from the first day hematologic response criteria were met, provided they were confirmed 28 days later until the date of PD or death. Median duration of OHR in the CML-AP/BP arm was not yet reached.

Arm/Group Title	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0	9
Median (Full Range) [Days]	104

22. Secondary Outcome

Title	Participants With Detectable Mutations of RNA (mRNA) of BCR-ABL at Baseline and at Best Achievement
Description	Detectable BCR-ABL transcripts (b3a2, b2a2 or minor) >=2.0 log copy/micrograms RNA, as measured by real-time quantitative PCR (RQ-PCR) at baseline and best achievement post-dose.
Time Frame	At baseline, every 12 weeks up to 2 years on study (including study CA180031/NCT00337454), every 24 weeks thereafter, and at discontinuation

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	30	11	13
Baseline	28 93.3%	11 100%	10 76.9%
Best Achievement	12 40%	7 63.6%	6 46.2%

23. Secondary Outcome

Title	Status of Point Mutations of BCR-ABL at Baseline (BL) and End of Study (EOS)
Description	Point mutations of BCR-ABL detected or undetected in the Quantitative real-time PCR polymerase chain reaction (RQ-PCR) products
Time Frame	At baseline and discontinuation--the study period was extended until the launch of dasatinib in Japan, January 2009.

Outcome Measure Data

Analysis Population Description

Treated participants

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	30	11	13
Undetectable at BL → Detectable at EOS	1 3.3%	1 9.1%	7 53.8%
Detectable at BL → Detectable at EOS	2 6.7%	1 9.1%	3 23.1%
Detectable at BL → Undetectable at EOS	2 6.7%	0 0%	0 0%
Detectable at BL → Not Analyzed at EOS	1 3.3%	1 9.1%	1 7.7%

24. Secondary Outcome

Title	Collection of Blood Samples for Pharmacokinetic Analysis of Dasatinib Twice Daily (BID) That Will Contribute to Population Pharmacokinetic Modeling
Description	Blood samples for pharmacokinetic analysis of Dasatinib BID that will contribute to population pharmacokinetic modeling were collected.
Time Frame	At any visit of later than Day 7, draw sample(s) at pretreatment trough (within 1 hour prior to dosing) or between 3 hours following treatment and prior to the next dose

Outcome Measure Data

Analysis Population Description

There was no individual PK analysis done for this study; analyses were integrated and evaluated as a part of population PK of this drug.

Arm/Group Title	CML - Chronic Phase (CML-CP)	CML - Accelerated Phase and Blast Phase (CML-AP/BP)	Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL)
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort who had completed the previous study (CA180031/NCT00337454) phase I/II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031(ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Imatinib resistant or intolerant CML-AP/BP disease cohort who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.	Ph+ ALL subjects with resistance or intolerance to past therapy and who had completed the previous study (CA180031/NCT00337454) phase II. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
Measure Participants	0	0	0

Adverse Events

Arm/Group Title	All Treated Participants
Arm/Group Description	Imatinib resistant or intolerant CML-CP disease cohort, Imatinib resistant or intolerant CML-AP/BP disease cohort, and Ph+ ALL subjects with resistance or intolerance to past therapy. The study drug was administered twice daily (BID). The starting dose level for this trial in each individual participant was the same dose level at the end of CA180031 (ie, 50mg, 70mg or 90mg BID on a continuous daily dosing schedule), allowed to modify within the range of 50 mg twice daily (BID) to 90 mg BID.
All Cause Mortality
	All Treated Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	All Treated Participants
	Affected / at Risk (%)	# Events
Total	33/54 (61.1%)
Blood and lymphatic system disorders
Febrile neutropenia	2/54 (3.7%)
Neutropenia	2/54 (3.7%)
Disseminated intravascular coagulation	1/54 (1.9%)
Leukopenia	1/54 (1.9%)
Thrombocytopenia	1/54 (1.9%)
Cardiac disorders
Atrial tachycardia	1/54 (1.9%)
Cardio-respiratory arrest	1/54 (1.9%)
Gastrointestinal disorders
Anal fistula	1/54 (1.9%)
Enterocolitis	1/54 (1.9%)
Gastrointestinal haemorrhage	1/54 (1.9%)
Haematochezia	1/54 (1.9%)
Haemorrhoids	1/54 (1.9%)
Ileus	1/54 (1.9%)
Periodontitis	1/54 (1.9%)
General disorders
Pyrexia	3/54 (5.6%)
Malaise	1/54 (1.9%)
Therapeutic response decreased	1/54 (1.9%)
Disease progression	1/54 (1.9%)
Infections and infestations
Pneumonia	6/54 (11.1%)
Enteritis infectious	2/54 (3.7%)
Cellulitis	1/54 (1.9%)
Gastroenteritis	1/54 (1.9%)
Perianal abscess	1/54 (1.9%)
Pseudomembranous colitis	1/54 (1.9%)
Enterocolitis infectious	1/54 (1.9%)
Injury, poisoning and procedural complications
Subdural haematoma	2/54 (3.7%)
Brain herniation	1/54 (1.9%)
Drug toxicity	1/54 (1.9%)
Fracture	1/54 (1.9%)
Haemothorax	1/54 (1.9%)
Overdose	1/54 (1.9%)
Contusion	1/54 (1.9%)
Investigations
Platelet count decreased	4/54 (7.4%)
Haemoglobin decreased	2/54 (3.7%)
Alanine aminotransferase increased	1/54 (1.9%)
Aspartate aminotransferase increased	1/54 (1.9%)
Haematocrit decreased	1/54 (1.9%)
Neutrophil count decreased	1/54 (1.9%)
Red blood cell count decreased	1/54 (1.9%)
White blood cell count decreased	1/54 (1.9%)
Metabolism and nutrition disorders
Anorexia	1/54 (1.9%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/54 (1.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	6/54 (11.1%)
Tumour lysis syndrome	2/54 (3.7%)
Colon cancer	1/54 (1.9%)
Malignant pleural effusion	1/54 (1.9%)
Blast cell crisis	1/54 (1.9%)
Lung neoplasm malignant	1/54 (1.9%)
Nervous system disorders
Cerebral haemorrhage	3/54 (5.6%)
Convulsion	1/54 (1.9%)
Subarachnoid haemorrhage	1/54 (1.9%)
Brain mass	1/54 (1.9%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/54 (5.6%)
Hypoxia	1/54 (1.9%)
Interstitial lung disease	1/54 (1.9%)
Pulmonary haemorrhage	1/54 (1.9%)
Pulmonary oedema	1/54 (1.9%)
Upper respiratory tract inflammation	1/54 (1.9%)
Skin and subcutaneous tissue disorders
Skin ulcer	1/54 (1.9%)
Vascular disorders
Haematoma	1/54 (1.9%)
Other (Not Including Serious) Adverse Events
	All Treated Participants
	Affected / at Risk (%)	# Events
Total	54/54 (100%)
Blood and lymphatic system disorders
Anaemia	23/54 (42.6%)
Febrile neutropenia	6/54 (11.1%)
Neutropenia	4/54 (7.4%)
Thrombocytopenia	3/54 (5.6%)
Cardiac disorders
Cardiomegaly	5/54 (9.3%)
Palpitations	5/54 (9.3%)
Pericardial effusion	4/54 (7.4%)
Sinus bradycardia	3/54 (5.6%)
Endocrine disorders
Hypothyroidism	3/54 (5.6%)
Eye disorders
Eyelid oedema	10/54 (18.5%)
Conjunctival haemorrhage	8/54 (14.8%)
Conjunctival hyperaemia	5/54 (9.3%)
Vision blurred	4/54 (7.4%)
Conjunctivitis	3/54 (5.6%)
Gastrointestinal disorders
Diarrhoea	32/54 (59.3%)
Nausea	21/54 (38.9%)
Constipation	18/54 (33.3%)
Vomiting	16/54 (29.6%)
Stomatitis	15/54 (27.8%)
Abdominal pain	7/54 (13%)
Toothache	7/54 (13%)
Abdominal distension	6/54 (11.1%)
Abdominal pain upper	6/54 (11.1%)
Cheilitis	5/54 (9.3%)
Gingivitis	5/54 (9.3%)
Haematochezia	5/54 (9.3%)
Abdominal pain lower	4/54 (7.4%)
Gingival bleeding	4/54 (7.4%)
Haemorrhoids	4/54 (7.4%)
Stomach discomfort	4/54 (7.4%)
Dental caries	3/54 (5.6%)
Gastrointestinal haemorrhage	3/54 (5.6%)
Gingival swelling	3/54 (5.6%)
General disorders
Pyrexia	27/54 (50%)
Malaise	23/54 (42.6%)
Oedema	18/54 (33.3%)
Oedema peripheral	9/54 (16.7%)
Face oedema	7/54 (13%)
Pain	7/54 (13%)
Chest pain	5/54 (9.3%)
Chills	5/54 (9.3%)
Chest discomfort	3/54 (5.6%)
Fatigue	3/54 (5.6%)
Hypothermia	3/54 (5.6%)
Immune system disorders
Seasonal allergy	3/54 (5.6%)
Infections and infestations
Nasopharyngitis	29/54 (53.7%)
Folliculitis	8/54 (14.8%)
Pharyngitis	6/54 (11.1%)
Bronchitis	5/54 (9.3%)
Gastroenteritis	4/54 (7.4%)
Infection	4/54 (7.4%)
Influenza	3/54 (5.6%)
Injury, poisoning and procedural complications
Excoriation	7/54 (13%)
Transfusion reaction	3/54 (5.6%)
Wound	3/54 (5.6%)
Investigations
Neutrophil count decreased	46/54 (85.2%)
Platelet count decreased	42/54 (77.8%)
White blood cell count decreased	41/54 (75.9%)
Blood lactate dehydrogenase increased	39/54 (72.2%)
Lymphocyte count decreased	39/54 (72.2%)
Aspartate aminotransferase increased	35/54 (64.8%)
Alanine aminotransferase increased	34/54 (63%)
Blood creatine phosphokinase increased	30/54 (55.6%)
Gamma-glutamyltransferase increased	25/54 (46.3%)
Haematocrit decreased	25/54 (46.3%)
Haemoglobin decreased	25/54 (46.3%)
Red blood cell count decreased	24/54 (44.4%)
Blood phosphorus decreased	24/54 (44.4%)
Blood albumin decreased	23/54 (42.6%)
Protein urine present	23/54 (42.6%)
White blood cell count increased	22/54 (40.7%)
Protein total decreased	20/54 (37%)
Blood alkaline phosphatase increased	19/54 (35.2%)
Weight increased	18/54 (33.3%)
Blood urine present	17/54 (31.5%)
Weight decreased	17/54 (31.5%)
Blood uric acid increased	16/54 (29.6%)
CD4 lymphocytes decreased	16/54 (29.6%)
Blood creatinine increased	12/54 (22.2%)
Blood urea increased	10/54 (18.5%)
Urinary sediment abnormal	10/54 (18.5%)
Reticulocyte count decreased	9/54 (16.7%)
Urobilin urine present	9/54 (16.7%)
Blood potassium decreased	8/54 (14.8%)
Electrocardiogram QT corrected interval prolonged	8/54 (14.8%)
Glucose urine present	8/54 (14.8%)
Protein urine	8/54 (14.8%)
Blood bilirubin increased	7/54 (13%)
Blood magnesium increased	7/54 (13%)
Blood potassium increased	7/54 (13%)
C-reactive protein increased	7/54 (13%)
Liver function test abnormal	7/54 (13%)
Lymphocyte count increased	6/54 (11.1%)
Neutrophil count increased	5/54 (9.3%)
CD4 lymphocytes increased	5/54 (9.3%)
Blood pressure increased	4/54 (7.4%)
Blood sodium decreased	4/54 (7.4%)
Prothrombin time prolonged	4/54 (7.4%)
Reticulocyte count increased	4/54 (7.4%)
Platelet count increased	4/54 (7.4%)
Activated partial thromboplastin time prolonged	3/54 (5.6%)
Blood chloride decreased	3/54 (5.6%)
Eosinophil count increased	3/54 (5.6%)
Urine ketone body present	3/54 (5.6%)
Metabolism and nutrition disorders
Anorexia	12/54 (22.2%)
Decreased appetite	6/54 (11.1%)
Hypophosphataemia	5/54 (9.3%)
Dehydration	3/54 (5.6%)
Hypokalaemia	3/54 (5.6%)
Musculoskeletal and connective tissue disorders
Myalgia	14/54 (25.9%)
Back pain	11/54 (20.4%)
Arthralgia	9/54 (16.7%)
Pain in extremity	9/54 (16.7%)
Musculoskeletal stiffness	4/54 (7.4%)
Joint swelling	3/54 (5.6%)
Musculoskeletal pain	3/54 (5.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	3/54 (5.6%)
Nervous system disorders
Headache	26/54 (48.1%)
Dizziness	7/54 (13%)
Hypoaesthesia	6/54 (11.1%)
Dysgeusia	5/54 (9.3%)
Psychiatric disorders
Insomnia	7/54 (13%)
Renal and urinary disorders
Haematuria	3/54 (5.6%)
Reproductive system and breast disorders
Gynaecomastia	4/54 (7.4%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	22/54 (40.7%)
Cough	21/54 (38.9%)
Dyspnoea	10/54 (18.5%)
Pharyngolaryngeal pain	8/54 (14.8%)
Epistaxis	6/54 (11.1%)
Rhinorrhoea	5/54 (9.3%)
Hypoxia	4/54 (7.4%)
Upper respiratory tract inflammation	4/54 (7.4%)
Skin and subcutaneous tissue disorders
Rash	27/54 (50%)
Erythema	8/54 (14.8%)
Haemorrhage subcutaneous	8/54 (14.8%)
Pruritus	8/54 (14.8%)
Purpura	8/54 (14.8%)
Acne	7/54 (13%)
Petechiae	5/54 (9.3%)
Eczema	4/54 (7.4%)
Skin exfoliation	4/54 (7.4%)
Dry skin	3/54 (5.6%)
Rash papular	3/54 (5.6%)
Vascular disorders
Hypertension	5/54 (9.3%)
Hypotension	4/54 (7.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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