ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00306202
Recruitment Status : Active, not recruiting
First Posted : March 23, 2006
Results First Posted : July 23, 2012
Last Update Posted : September 26, 2017
Sponsor:
Collaborator:
Innovative Therapies For Children with Cancer Consortium
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia
Intervention Drug: Dasatinib
Enrollment 63

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Period Title: Overall Study
Started 17 [1] 17 [2] 24 [3]
Completed 11 [4] 16 [4] 24 [4]
Not Completed 6 1 0
Reason Not Completed
Still on treatment             6             1             0
[1]
Started = Treated. 18 were enrolled; 1 no longer met study criteria and was never treated
[2]
Started=Treated. 20 were enrolled;3 never treated(2 no longer met study criteria;1 withdrew consent)
[3]
Started = Treated. 24 were enrolled; 1 no longer met study criteria and was never treated
[4]
Completed = Off-treatment
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose Total
Hide Arm/Group Description

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained. Total of all reporting groups
Overall Number of Baseline Participants 17 17 24 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 17 participants 17 participants 24 participants 58 participants
12.4  (4.1) 9.7  (4.3) 8.6  (5.6) 10.0  (5.0)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
< 2 0 0 2 2
Between 2 and 6 years 2 5 7 14
Between 7 and 11 years 6 5 7 18
Between 12 and 18 years 9 7 7 23
> 18 0 0 1 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
Female
6
  35.3%
5
  29.4%
8
  33.3%
19
  32.8%
Male
11
  64.7%
12
  70.6%
16
  66.7%
39
  67.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
White 16 15 21 52
Black/African American 0 0 1 1
Asian 1 1 1 3
Other 0 1 1 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
Not Hispanic/Latino 0 1 0 1
Not Reported 17 16 24 57
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
France 6 4 5 15
Austria 0 0 3 3
Netherlands 2 5 6 13
Germany 3 2 3 8
Italy 1 2 5 8
United Kingdom 5 4 2 11
Extramedullary Disease Involvement   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
Outside Spleen or Liver (involvement of CNS) 0 5 6 11
Spleen (participants with splenomegaly) 0 2 2 4
Liver (participants with hepatomegaly) 1 4 1 6
[1]
Measure Description: Participants could be categorized in more than 1 category. CNS = central nervous system
White Blood Cells in Peripheral Blood  
Median (Full Range)
Unit of measure:  Cells/mm^3
Number Analyzed 17 participants 17 participants 24 participants 58 participants
8.7
(3.6 to 134.6)
6.2
(0.6 to 197.0)
3.0
(0.7 to 20.0)
5.8
(0.6 to 197.0)
White Blood Cells in Peripheral Blood  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
< 20000/mm^3 16 12 22 50
>=20000/mm^3 1 5 2 8
Hemoglobin in Peripheral Blood  
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 17 participants 17 participants 24 participants 58 participants
12.2
(9.5 to 16.0)
10.0
(7.7 to 13.5)
10.2
(7.1 to 13.6)
11.0
(7.1 to 16.0)
Platelets in Peripheral Blood  
Median (Full Range)
Unit of measure:  Cells/mm^3
Number Analyzed 17 participants 17 participants 24 participants 58 participants
294.0
(139.0 to 1058.0)
82.0
(3.0 to 312.0)
41.0
(3.0 to 226.0)
86.0
(3.0 to 1058.0)
Basophils in Peripheral Blood   [1] 
Median (Full Range)
Unit of measure:  Percentage of participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
0.9
(0.0 to 9.0)
0.2
(0.0 to 4.5)
0.0
(0.0 to 2.0)
0.0
(0.0 to 9.0)
[1]
Measure Description: n = 9, 10, 19; n = number of participants with measures available
Basophils in Bone Marrow   [1] 
Median (Full Range)
Unit of measure:  Percentage
Number Analyzed 17 participants 17 participants 24 participants 58 participants
0.6
(0.0 to 2.0)
0.0
(0.0 to 0.2)
0.0
(0.0 to 0.8)
0.0
(0.0 to 2.0)
[1]
Measure Description: n = 13, 12, 19; n = number of participants with measures available
Blasts in Peripheral Blood   [1] 
Median (Full Range)
Unit of measure:  Percentage of participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
0.0
(0.0 to 1.0)
0.0
(0.0 to 88.0)
18.0
(0.0 to 92.0)
2.5
(0.0 to 92.0)
[1]
Measure Description: n = 9, 9, 19; n = number of participants with measures available
Blasts in Bone Marrow   [1] 
Median (Full Range)
Unit of measure:  Percentage
Number Analyzed 17 participants 17 participants 24 participants 58 participants
0.0
(0.0 to 4.0)
39.0
(0.0 to 95.0)
79.9
(24.0 to 98.0)
52.0
(0.0 to 98.0)
[1]
Measure Description: n = 15, 16, 24; n = number of participants with measures available.
Promyelocytes in Bone Marrow   [1] 
Median (Full Range)
Unit of measure:  Percentage
Number Analyzed 17 participants 17 participants 24 participants 58 participants
3.0
(0.0 to 43.0)
0.5
(0.0 to 6.0)
0.4
(0.0 to 4.0)
0.8
(0.0 to 43.0)
[1]
Measure Description: n = 12, 12, 19; n = number of participants with measures available
Lansky Play Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
<60 0 0 0 0
60 - 70 1 2 3 6
80 - 90 1 2 3 6
100 7 4 2 13
Not Reported 8 9 16 33
[1]
Measure Description:

Used in children between 1 to 16 years of age to measure functional impairment. Scores range from 0-100 units on a scale; lower the score, worse the survival.

10-40:Moderate to severe restriction. 50:Gets dressed but inactive much of day; no active play, able to participate in quiet play. 60:Out of bed, but minimal active play; keeps busy with quiet activities. 70:Substantial restriction of, and less time spent, in play. 80:Active, but tires quickly. 90:Minor restrictions in physically strenuous activity. 100: Fully active, normal. Not reported=no Karnofsky Performance Score reported.

Karnofsky Performance Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 17 participants 17 participants 24 participants 58 participants
<60 0 0 0 0
60 - 70 0 1 1 2
80 - 90 1 4 11 16
100 7 4 4 15
Not Reported 9 8 8 25
[1]
Measure Description:

Classifies patients according to their functional impairment. Scores range from 0-100 units on a scale, the lower the score, the worse the survival for most serious illnesses.

<=60: Needs increasing assistance up to Death (0). 70: Cares for self. Unable to carry on normal activity or to do active work. 80: Normal activity with effort; some signs or symptoms of disease. 90: Able to carry on normal activities; minor signs or symptoms of disease. 100: Normal, no complaints. Not reported=no Lansky Play Score reported.

1.Primary Outcome
Title Recommended Phase II Dose of Dasatinib in Children and Adolescents With Relapsed or Refractory Leukemia
Hide Description The recommended phase 2 dasatinib dose was determined based on efficacy, safety, and pharmacokinetic data obtained at the prespecified dose levels.
Time Frame From the date of first dose to end-of-treatment (EOT) (Median duration of therapy in months: Stratum 1=24.11 [Range:2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least 1 dose of study therapy
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2, escalated/dose level 3 of 100 mg/m^2, escalated/dose level 3 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 17 17 24
Measure Type: Number
Unit of Measure: mg/m^2 QD
60 80 NA [1] 
[1]
Phase II dose was not chosen for this population as there is no current plan to move forward with development in this population due to lack of efficacy despite escalations to the highest dose of 120 mg/m^2 in this trial.
2.Secondary Outcome
Title Number of Participants With Related Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0.
Hide Description

AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization.

Grade 3 = Severe; Grade 4 = Life-threatening or disabling.

Time Frame From the date of first dose until at least 30 days after the last dose of study drug (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 11 6 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
Drug-Related Deaths 0 0 0 0 0 0 0 0
Drug-Related SAEs 1 1 2 3 2 2 2 2
Drug-Related AEs Leading to Discontinuation 0 0 0 0 1 0 1 0
Grade 3/4 AEs 4 2 3 3 2 4 2 2
3.Secondary Outcome
Title Number of Participants With Dose-limiting Toxicity (DLT)
Hide Description

DLTs: AEs which were at least possibly drug-related occurring within first 3 weeks of dasatinib therapy (toxicities occurring after 21 days were also considered) and are:-

  • Any nonhematologic clinically-apparent toxicity of Grade(GR)≥3 occurring despite appropriate medical management and GR4 laboratory abnormality/GR3 lasting ≥7 days
  • GR4 neutropenia or thrombocytopenia lasting ≥7 days and not explained by the presence of leukemia after hematopoietic reconstitution
  • Any clinically important toxicity of GR≥2 requiring treatment discontinuation or interruption ≥7 days.
Time Frame From the date of first dose until at least 30 days after the last dose of study drug (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 11 6 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
0 0 0 0 1 0 0 1
4.Secondary Outcome
Title Number of Participants With Hematology Abnormalities by NCI CTCAE Version 3.0
Hide Description GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. WBC: GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. ANC: GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Hemoglobin: GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL; GR4=<6.5g/dL. Platelets: GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L; GR4=<25.0*10^9/L.
Time Frame Days 8, 15, 22, 29, 36, 43, then every 3 weeks, then every 3 months after 1 Year, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 11 6 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
WBC GR1 6 4 2 1 1 1 0 0
WBC GR2 0 1 3 3 0 1 1 1
WBC GR3 0 0 0 1 0 2 1 0
WBC GR4 0 0 1 3 2 2 3 1
ANC GR1 3 3 1 1 0 0 0 0
ANC GR2 4 0 2 2 1 0 0 0
ANC GR3 1 2 2 0 0 2 0 2
ANC GR4 0 1 3 4 4 4 6 3
Platelet GR1 4 4 0 2 0 0 0 0
Platelet GR2 0 1 0 2 1 0 0 0
Platelet GR3 2 0 4 1 0 1 1 1
Platelet GR4 0 0 4 3 4 5 5 5
Hemoglobin GR1 3 4 1 0 0 0 0 0
Hemoglobin GR2 4 1 5 3 2 3 3 3
Hemoglobin GR3 0 0 1 4 3 1 3 2
Hemoglobin GR4 0 0 1 0 0 2 0 0
5.Secondary Outcome
Title Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) by NCI CTCAE Version 3.0
Hide Description GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Low calcium: GR1=<LLN–8.0 mg/dL, GR2=<8.0–7.0 mg/dL, GR3=<7.0–6.0 mg/dL, GR4=<6.0 mg/dL; Low magnesium: GR1=<LLN–1.2 mg/dL, GR2=<1.2–0.9 mg/dL, GR3=<0.9–0.7 mg/dL, GR4=<0.7 mg/dL; Low phosphate: GR1=<LLN – 2.5 mg/dL, GR2=<2.5 – 2.0 mg/dL, GR3=<2.0 – 1.0 mg/dL, GR4=<1.0 mg/dL.
Time Frame Days 22 and 43, then every 12 weeks, then every 24 weeks after 24 months of treatment, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 11 6 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
Low Calcium GR1 3 0 2 2 2 0 1 0
Low Calcium GR2 0 0 1 1 0 2 2 1
Low Calcium GR3 0 0 0 0 0 0 1 0
Low Calcium GR4 0 0 0 0 0 0 0 0
Low magnesium GR1 1 1 5 0 1 0 4 1
Low Magnesium GR2 0 0 0 0 0 0 0 0
Low Magnesium GR3 0 0 0 0 0 0 0 0
Low Magnesium GR4 0 0 0 0 0 0 0 0
Low Phosphate GR1 2 1 2 2 0 2 2 1
Low Phosphate GR2 1 0 0 1 0 2 1 1
Low Phosphate GR3 0 0 0 0 1 0 1 1
Low Phosphate GR4 0 0 0 0 0 0 0 0
6.Secondary Outcome
Title Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) by NCI CTCAE Version 3.0
Hide Description GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. AST and ALT: GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4:>20.0*ULN. Total bilirubin:GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN.
Time Frame Days 22 and 43, then every 12 weeks, then every 24 weeks after 24 months of treatment, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 11 6 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
AST GR1 1 3 5 3 1 4 2 2
AST GR2 0 0 2 1 1 1 1 1
AST GR3 0 0 1 2 1 1 0 0
AST GR4 0 0 0 0 0 0 0 0
High ALT GR1 4 4 4 2 0 2 3 2
High ALT GR2 0 0 2 1 1 2 1 0
High ALT GR3 0 0 1 0 1 2 0 1
High ALT GR4 0 0 0 2 0 0 0 0
Total Bilirubin GR1 2 0 1 1 0 1 2 0
Total Bilirubin GR2 0 1 0 0 1 2 1 1
Total Bilirubin GR3 1 0 0 0 0 0 0 0
Total Bilirubin GR4 0 0 0 0 0 0 0 0
High Serum Creatinine GR1 1 1 1 1 1 0 0 0
High Serum Creatinine GR2 0 0 1 0 0 0 1 0
High Serum Creatinine GR3 0 0 0 0 0 0 0 0
High Serum Creatinine GR4 0 0 0 0 0 0 0 0
7.Secondary Outcome
Title Number of Participants With Major Cytogenetic Response (MCyR) at Any Time in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Hide Description

Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated.

MCyR: A cytogenetic response that is either complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR).

CCyR: 0% Ph+ cells in metaphase in BM. PCyR: >0% to 35% Ph+ cells in metaphase in BM.

Time Frame Strata 1 and 2/3: At Week 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Week 4, 19, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in strata 1 and 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Ph+ chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 6 8 9
Measure Type: Number
Unit of Measure: participants
9 6 4 7
8.Secondary Outcome
Title Number of Participants With Major Cytogenetic Response (MCyR) in Stratum 1 (Ph+ CP-CML) Within First 12 and 24 Weeks
Hide Description

Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated.

MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: >0% to 35% Ph+ cells in metaphase in BM.

Time Frame After completion of Week 12 and 24 (measured at Weeks 13 and 25)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 1: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Ph+ chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 6
Measure Type: Number
Unit of Measure: participants
MCyR within first 12 weeks 6 2
MCyR within first 24 weeks 9 5
9.Secondary Outcome
Title Best Cytogenetic Response (CyR) in Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Hide Description

Best CyR was assessed based on the percentages of Ph+ metaphases of ≥20 analyzed metaphases in BM sample.

Participants with complete, partial, minor, minimal, or no CyR. Refer to Outcome Measure 7 for definitions of CCyR and PCyR. Minor CyR:>35%-65% Ph+ cells in metaphase in BM. Minimal CyR:>65%-95% Ph+ cells in metaphase in BM. No CyR:>95%-100% Ph+ cells in metaphase in BM. Unable to determine:Participants without valid cytogenetic assessment (i.e., at least 1 metaphase observed and number of Ph+ metaphases smaller than total number of metaphases [%Ph+ <100%]).

Time Frame Strata 1 and 2/3: At Weeks 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Weeks 4, 19, 25, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants (strata 1 and 2/3): Participants who received at least 1 dose of study therapy.

Stratum 2/3 dasatinib 80 mg/m^2 dose cohort includes 1 participant as having a CCyR due to a data entry error that was fixed after database lock for this study.

Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 6 8 9
Measure Type: Number
Unit of Measure: participants
No Response (>95% - 100%) 1 0 0 1
Minimal (>65% - 95%) 0 0 0 0
Minor (>35% - 65%) 1 0 0 0
Partial (>0% - 35%) 1 0 0 0
Complete (0%) 8 6 4 8
Unable to determine 0 0 4 0
10.Secondary Outcome
Title Percentage of Participants With Complete Cytogenetic Response (CCyR) or Major Cytogenetic Response (MCyR) at Recommended Phase II Dose
Hide Description

Cytogenetic responses were based on the karyotype analysis of the percentage of Ph+ metaphases among cells in metaphase on a BM sample. At least 20 metaphase cells from a BM sample were evaluated.

MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: >0% to 35% Ph+ cells in metaphase in BM.

Time Frame Strata 1 and 2/3: At Week 7, 13, then every 12 weeks, and EOT; Stratum 2/3: Additionally at Week 4, 19, 31 (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in strata 1 and 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CCyR
72.7
(39.0 to 94.0)
88.9
(51.8 to 99.7)
MCyR
81.8
(48.2 to 97.7)
88.9
(51.8 to 99.7)
11.Secondary Outcome
Title Time to Major Cytogenetic Response (MCyR) in Responders: Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Hide Description Defined as time (in days) from the first dose of dasatinib until criteria were first met for MCyR. MCyR: A CyR that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: >0% to 35% Ph+ cells in metaphase in BM. The Kaplan-Meier plot was used. A 2-sided, 95% confidence interval (CI) for the median was computed using the Brookmeyer and Crowley method.
Time Frame Strata 1 and 2/3: At Weeks 7, 13, 25, 37, then every 12 weeks; Stratum 2/3: Additionally at Weeks 4, 19, 31; until first MCyR (maximum participant time to first MCyR of 92 days).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who had cytogenetic response. Participants with at least 1 metaphase observed & the number of Ph+ metaphases smaller than the total number of metaphases [%Ph+ <100%]) were considered responders.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 15 12
Median (95% Confidence Interval)
Unit of Measure: days
75.0
(43.0 to 92.0)
33.5
(22.0 to 43.0)
12.Secondary Outcome
Title Duration of Major Cytogenetic Response (MCyR) in Responders (Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML])
Hide Description

Defined as the time (in months) from the first day that all criteria were met for MCyR until the date of progression (based on the Investigator’s assessment) or death (for participants whose best responses were MCyR and CCyR respectively).

MCyR: A cytogenetic response that was either CCyR or PCyR. CCyR: 0% Ph+ cells in metaphase in BM. PCyR: >0% to 35% Ph+ cells in metaphase in BM. The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.

Time Frame From the date of first MCyR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 48.6 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who had cytogenetic response. Participants with at least 1 metaphase observed & the number of Ph+ metaphases smaller than the total number of metaphases [%Ph+ <100%]) were considered responders. Participants who neither progressed nor died were censored on the date of their last valid cytogenetic assessment.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 1 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 15 12
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(11.8 to NA)
4.6
(2.1 to 17.4)
[1]
Median duration of MCyR was not estimable as only 5 participants had disease progression and more than 50% of participants were censored.
13.Secondary Outcome
Title Duration of Complete Cytogenetic Response (CCyR) in Responders: Stratum 1 [Ph+ CP-CML] and Stratum 2/3 [Ph+ ALL or AP/BP-CML]
Hide Description

Defined as time (in months) from the first day that all criteria were met for CCyR until the date of progression (based on the Investigator’s assessment) or death (for participants whose best response was CCyR).

CCyR = 0% Ph+ metaphases of ≥ 20 analyzed metaphases in BM aspiration. The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.

Time Frame From the date of first CCyR assessment to date of progression, death, or last tumor assessment (maximum participant duration of response of 45.1 months)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants who had cytogenetic response. Participants with at least 1 metaphase observed & the number of Ph+ metaphases smaller than the total number of metaphases [%Ph+ <100%]) were considered responders. Participants who neither progressed nor died were censored on the date of their last valid cytogenetic assessment.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 14 12
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(11.8 to NA)
4.6
(2.1 to 17.4)
[1]
Median duration of CCyR was not estimable as only 5 participants had disease progression and more than 50% of participants were censored.
14.Secondary Outcome
Title Number of Participants With Major Hematologic Response (MaHR) at Any Time in Stratum 2/3 (Ph+ ALL or AP/BP-CML) and Stratum 4 (Ph- ALL/AML)
Hide Description

Defined as participants having as best response complete hematologic response (CHR) or CHR with incomplete platelet recovery (CHRp).

Criteria:

CHR-WBC in Peripheral Blood (PB):≤ULN; Immature cells in PB:No blasts, promyelocytes, myelocytes, metamyelocytes; Platelet count (untransfused):≥100,000/mm^3 and ≤450,000/mm^3; ANC:≥ 1000/mm^3; Blasts in BM:<5%; Extra medullary disease:No extramedullary leukemia, including no hepato or splenomegaly (regardless of CNS involvement).

CHRp-CHR except platelet count (untransfused) & ANC:20,000/mm^3 ≤platelet <100,000/mm^3 & /or 500/mm^3 ≤ANC ≤1000/mm^3.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 4, 7, 13, 19, 25, 31, 37; at Week 10 (only stratum 4); then every 12 weeks upto 24 months; then once/year; EOT(Median duration of therapy in months: Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in strata 2/3 and 4: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 8 9 6 6 6 6
Measure Type: Number
Unit of Measure: participants
2 6 0 0 0 0
15.Secondary Outcome
Title Number of Participants With Major Hematologic Response (MaHR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML) Within First 6 and 24 Weeks
Hide Description

Defined as participants having as best response a CHR or CHRp.

Criteria:

CHR-WBC in PB:≤ULN; Immature cells in PB:No blasts, promyelocytes, myelocytes, metamyelocytes; Platelet count (untransfused):≥100,000/mm^3 and ≤450,000/mm^3; ANC:≥ 1000/mm^3; Blasts in BM:<5%; Extra medullary disease:No extramedullary leukemia, including no hepato or splenomegaly (regardless of CNS involvement).

CHRp-CHR except platelet count (untransfused) and ANC:20,000/mm^3 ≤platelet <100,000/mm^3 and /or 500/mm^3 ≤ANC ≤1000/mm^3.

Time Frame After completion of Week 6 and 24 (measured at weeks 7 and 25)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Stratum 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 8 9
Measure Type: Number
Unit of Measure: participants
MaHR within first 6 weeks 2 5
MaHR within first 24 weeks 2 6
16.Secondary Outcome
Title Best Hematologic Response (HR) At Any Time: Stratum 1 (Ph+ CP-CML)
Hide Description

HR: Determined by complete blood count (CBC), differential, and platelet count (PLT). Criteria for complete hematologic response (CHR):

WBC in PB: <10,000/mm^3; Immature cells in PB: No blasts or promyelocytes (myelocytes + metamyelocytes) <5%; Basophils in PB: <5%; Platelet count (untransfused): <450,000/mm^3; Extra medullary disease: No extramedullary leukemia, including no splenomegaly.

Unconfirmed HR = All criteria met. Confirmed HR = Criteria for HR fulfilled again at least 28 days after they first met with no concomitant use of anagrelide or hydroxyurea during this interval.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 7, 13, 25, 37; then every 12 weeks upto 24 months; then once/year; EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 1: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 6
Measure Type: Number
Unit of Measure: participants
Best Confirmed HR-Complete 10 6
Best Confirmed HR-No Response 1 0
Best Unconfirmed Hematologic Response-Complete 10 6
Best Unconfirmed Hematologic Response-No Response 1 0
17.Secondary Outcome
Title Best Hematologic Response (HR) At Any Time: Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Hide Description

HR was determined by CBC, differential, and platelet count. Refer to outcome measure 15 for criteria for CHR and CHRp. Criteria for minor hematologic response (MiHR): CHRp except blasts in BM-≥5% and ≤15% blasts in BM.

Unconfirmed HR = All criteria met. periph=peripheral. Confirmed HR = Criteria for HR fulfilled again at least 28 days after they first met with no concomitant use of anagrelide or hydroxyurea during this interval.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 4, 7, 13, 19, 25, 31, 37; then every 12 weeks up to 24 months; then once/year; EOT (Median duration of therapy in months: Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Stratum 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 8 9
Measure Type: Number
Unit of Measure: participants
Best Confirmed HR-Complete 1 5
Best Confirmed HR-Complete except periph. recovery 1 1
Best Confirmed HR-No Response 6 3
Best Unconfirmed HR-Complete 3 7
Best Unconfirmed HR-Minor 0 1
Best Unconfirmed HR-No Response 5 1
18.Secondary Outcome
Title Best Hematologic Response (HR) At Any Time: Stratum 4 (Ph- ALL/AML)
Hide Description HR was determined by CBC, differential, and platelet count. Unable to determine = Participants without any valid hematologic assessments.
Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 4, 7, 10, 13, 19, 25, 31, 37; then every 12 weeks upto 24 months; then once/year; EOT (Median duration of therapy in months: Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 4: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 4 Ph- ALL/AML (Dasatinib 60 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 80 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 100 mg/m^2) Stratum 4 Ph- ALL/AML (Dasatinib 120 mg/m^2)
Hide Arm/Group Description:
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 6 6 6 6
Measure Type: Number
Unit of Measure: participants
Best Confirmed HR-No Response 5 6 6 6
Best Confirmed HR-Unable to Determine 1 0 0 0
Best Unconfirmed HR-No Response 5 6 6 6
Best Unconfirmed HR-Unable to Determine 1 0 0 0
19.Secondary Outcome
Title Time to Major Hematologic Response (MaHR): Stratum 2/3 (PH+ ALL or AP/BP-CML)
Hide Description

Defined as time (in days) from first dose of dasatinib until the first day MaHR criteria were met, provided they were confirmed later (after 28 days) with no concomitant use of anagrelide or hydroxyurea during this interval.

MaHR: Defined as participants having as best response a CHR or CHRp. Refer to Outcome Measure 15 for criteria for CHR and CHRp. Estimated by the Kaplan-Meier method and a 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 4, 7, 13, 19, 25, 31, 37; then every 12 weeks upto 24 months; then once/year; until confirmed MaHR (maximum participant time to first MaHR of 44 days).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated participants with MaHR in stratum 2/3.
Arm/Group Title Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 8
Median (95% Confidence Interval)
Unit of Measure: days
36.0
(29.0 to 42.0)
20.Secondary Outcome
Title Time to Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML)
Hide Description

Time to CHR is the time (in days) from first dose of dasatinib until the first day CHR criteria were met, provided they were confirmed later after 28 days with no concomitant use of anagrelide or hydroxyurea during this interval.

Refer to Outcome Measure 16 for criteria to CHR in Stratum 1 and to Outcome Measure 15 for criteria for CHR in Stratum 2/3.

Estimated by the Kaplan-Meier method and a 2-sided 95% CI for median was computed using the Brookmeyer and Crowley method.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 7, 13, 25, 37; at Week 4, 19, 31 (only stratum 2/3); then every 12 weeks upto 24 months; then once/year; until criteria was first met for CHR (maximum participant time to first CHR of 65 days).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants with CHR in strata 1 and 2/3.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 16 6
Median (95% Confidence Interval)
Unit of Measure: days
21.5
(16.0 to 23.0)
39.5
(36.0 to 44.0)
21.Secondary Outcome
Title Duration of Major Hematologic Response (MaHR): Stratum 2/3 (Ph+ALL or AP/BP-CML)
Hide Description

Duration of MaHR is the time (in months) from the first day criteria were met for MaHR, provided they were confirmed later at least after 28 days with no concomitant use of anagrelide or hydroxyurea during this interval, until death or progression was first observed.

MaHR: Defined as participants having as best response a CHR or CHRp. Refer to outcome measure 20 for criteria for CHR or CHRp. The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.

Time Frame From the date of first confirmed MaHR to date of progression, death, or last tumor assessment (maximum participant duration of response of 37 months).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants with MaHR in stratum 2/3. Participants who neither discontinued due to progression nor progressed nor died were censored on the date of their last hematologic or cytogenetic assessment, whichever came last.
Arm/Group Title Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 8
Median (95% Confidence Interval)
Unit of Measure: months
4.4 [1] 
(3.5 to NA)
[1]
Upper limit could not be derived with the method of Brookmeyer and Crowley.
22.Secondary Outcome
Title Duration of Complete Hematologic Response (CHR): Stratum 1 (Ph+ CP-CML) and Stratum 2/3 (Ph+ALL or AP/BP-CML)
Hide Description

Duration of CHR is the time (in months) from the first day criteria were met for CHR, provided they were confirmed later (after 28 days) with no concomitant use of anagrelide or hydroxyurea during this interval until death or progression was first observed. Refer to Outcome Measure 20 for criteria for CHR (Stratum 1) and Outcome Measure 19 for CHR (Stratum 2/3).

The Kaplan-Meier plot was used. A 2-sided, 95% CI for the median was computed using the Brookmeyer and Crowley method.

Time Frame From the date of first confirmed CHR to date of progression, death, or last tumor assessment (maximum participant duration of response of 50 months).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Treated participants with CHR in strata 1 and 2/3. Participants who neither discontinued due to progression nor progressed nor died were censored on the date of their last hematologic or cytogenetic assessment, whichever came last.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 16 6
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(14.3 to NA)
7.3 [2] 
(3.5 to NA)
[1]
Median duration of CHR was not estimable as only 5 participants had disease progression and more than 50% of participants were censored.
[2]
Upper limit could not be derived with the method of Brookmeyer and Crowley.
23.Secondary Outcome
Title Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 1 (Ph+ CP-CML)
Hide Description

A participant was said to have a confirmed HR if all the criteria for HR were fulfilled again at least 28 days after they first met with no concomitant use of anagrelide or hydroxyurea during this interval.

HR observed in stratum 1 was CHR. Refer to Outcome Measure 20 for criteria for CHR.

The Clopper and Pearson method was used to compute 95% exact CIs.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 7, 13, 25, 37; then every 12 weeks upto 24 months; then once/year; EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 1 who received at least 1 dose of dasatinib 60 mg/m^2.
Arm/Group Title Stratum1 Ph+ CP-CML (Dasatinib 60 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
90.9
(58.7 to 99.8)
24.Secondary Outcome
Title Percentage of Participants With Confirmed Hematologic Response (HR) at Recommended Phase II Dose: Stratum 2/3 (Ph+ALL or AP/BP-CML)
Hide Description

A participant is said to have a confirmed HR if criteria for HR were fulfilled again at least 28 days after they first met with no concomitant use of anagrelide or hydroxyurea during this interval.

Confirmed HR observed in stratum 2/3 was either CHR or MaHR or overall hematologic response (OHR).

Refer to Outcome Measure 19 for criteria for CHR and MaHR. OHR is defined as MaHR or MiHR. MiHR=CHRp except blasts in BM (≥ 5% and ≤ 15% blasts in BM). The Clopper and Pearson method was used to compute 95% exact CIs.

Time Frame Days 8, 15, 22, 29, 36, 43; Weeks 4, 7, 13, 19, 25, 31, 37; then every 12 weeks upto 24 months; then once/year; EOT (Median duration of therapy in months: Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 2/3: Participants who received at least 1 dose of dasatinib 80 mg/m^2.
Arm/Group Title Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 9
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
CHR
55.6
(21.2 to 86.3)
MaHR
66.7
(29.9 to 92.5)
OHR
66.7
(29.9 to 92.5)
25.Secondary Outcome
Title Number of Participants With Molecular Responses in Stratum 1 (Ph+ CP-CML)
Hide Description

Molecular response was calculated by measuring p210 variant of BCR-ABL transcripts in blood during treatment using quantitative polymerase chain reaction (qPCR) assay.

Major molecular response (MMR): Ratio of the BCR-ABL to ABL <10^-3 or 0.1% on the international scale.

Complete molecular response (CMR): Complete absence of BCR-ABL or the ratio is <10^-4.5 or 0.00316% on the international scale.

Confirmed MMR or CMR = Criteria met again >6 weeks. BCR-ABL=the fused gene found in participants with this type of CML.

Time Frame At baseline (within 3 weeks before initiation of study therapy), After hematologic response, EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 1: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 1 Ph+ CP-CML (Dasatinib 60 mg/m^2) Stratum 1 Ph+ CP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 11 6
Measure Type: Number
Unit of Measure: participants
MMR (Overall) 6 2
CMR (Unconfirmed) 3 1
CMR (Confirmed) 1 0
26.Secondary Outcome
Title Number of Participants With Major Molecular Response (MMR) in Stratum 2/3 (Ph+ ALL or AP/BP-CML)
Hide Description

Molecular response was calculated by measuring BCR-ABL transcripts in blood during treatment using qPCR assay.

MMR: Ratio of the BCR-ABL to ABL <10^-3 or a ≥3 log reduction from baseline in participants with p190 variant; ratio of the BCR-ABL to ABL <10^-3 on the international scale in participants with p210 variant.

BCR-ABL=the fused gene found in participants with this type of CML.

Time Frame At baseline (within 3 weeks before initiation of study therapy), After hematologic response, EOT (Median duration of therapy in months: Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants (14 with p190 variant and 3 with p210 variant BCR-ABL transcripts) in stratum 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 60 mg/m^2) Stratum 2/3 Ph+ ALL or AP/BP-CML (Dasatinib 80 mg/m^2)
Hide Arm/Group Description:

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 8 9
Measure Type: Number
Unit of Measure: participants
2 6
27.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description

Time in months from 1st first dose until progression (resistance or refractory disease) or death was first documented by investigator.

Progressive disease: Resistant disease for which investigator may electively stop treatment or refractory disease requiring cessation of study treatment.

The PFS was estimated using the Kaplan-Meier product-limit method, and a two-sided 95% CI for the median PFS time was computed using the method of Brookmeyer and Crowley.

Time Frame From the date of randomization to date of progression, death, last tumor assessment, or 5 years after EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants: Participants who received at least 1 dose of study therapy.

If no progression or death was reported, PFS was censored at the last assessment date done on-study (i.e., up to 30 days after last dosing date) at which non-progression was reported.

Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2.

QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 17 17 24
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(14.8 to NA)
4.9
(1.2 to 8.4)
1.4
(0.5 to 1.6)
[1]
Median PFS was not estimable as only 6 of the 17 participants progressed.
28.Secondary Outcome
Title Overall Survival (OS)
Hide Description Defined as time in months from start of study therapy to death. The OS was estimated using the Kaplan-Meier product-limit method, and a two-sided 95% CI for the median OS time was computed using the Brookmeyer and Crowley method.
Time Frame From start of study therapy until death or 5 years after EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least 1 dose of study therapy. Participants lost to followup were censored on the last date the participant was known to be alive.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 17 17 24
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
8.6
(3.9 to 22.5)
3.0
(1.9 to 4.4)
[1]
Median OS was not estimable as 14 of the 17 participants were censored by 25 May 2011 (Last Subject Last Observation).
29.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) by Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 QD Starting Dose
Hide Arm/Group Description:

Stratum 1 (Ph+ CP-CML): Participants with imatinib-resistant Ph+ CML in CP; Stratum 2/3 (PH+ ALL OR AP/BP-CML): Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in AP, or in MBP, or in LBP; or relapsed or refractory Ph+ ALL after imatinib use; or second or subsequent relapse of Ph+ AML; Stratum 4 (PH- ALL/AML): Participants with second or subsequent relapse of Ph- ALL or Ph- AML.

Strata 1, 2/3, and 4: 60 mg/m^2 starting dose; 80 mg/m^2 escalated/dose level 2; Stratum 4: 100 mg/m^2 escalated/dose level 3 and 120 mg/m^2 escalated/dose level 4. QD, as long as clinical benefit was observed.

Overall Number of Participants Analyzed 53
Median (Full Range)
Unit of Measure: hours
Infants and Toddlers (age<2 years old; n=2)
0.5
(0.5 to 0.5)
Children (age>=2 and <12 years old; n=43)
1.1
(0.5 to 4.1)
Adolescents (age>=12 and <18 years old; n=28)
1.0
(0.5 to 6.0)
Above 18 Years (n=1)
0.9
(0.9 to 0.9)
Total (n=74)
1.0
(0.5 to 6.0)
30.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 QD Starting Dose
Hide Arm/Group Description:

Stratum 1 (Ph+ CP-CML): Participants with imatinib-resistant Ph+ CML in CP; Stratum 2/3 (PH+ ALL OR AP/BP-CML): Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in AP, or in MBP, or in LBP; or relapsed or refractory Ph+ ALL after imatinib use; or second or subsequent relapse of Ph+ AML; Stratum 4 (PH- ALL/AML): Participants with second or subsequent relapse of Ph- ALL or Ph- AML.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Strata 1, 2/3, and 4: 60 mg/m^2 starting dose; 80 mg/m^2 escalated/dose level 2; Stratum 4: 100 mg/m^2 escalated/dose level 3 and 120 mg/m^2 escalated/dose level 4. QD, as long as clinical benefit was observed.

Overall Number of Participants Analyzed 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours
Infants and Toddlers (age<2 years old; n=2)
2.1
(24.0%)
Children (age>=2 and <12 years old; n=36)
3.0
(62.8%)
Adolescents (age>=12 and <18 years old; n=22)
3.8
(43.9%)
Above 18 years (n=1)
7.3 [1] 
(NA%)
Total (n=61)
3.3
(55.7%)
[1]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
31.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Observed Maximum Plasma Concentration (Cmax) by Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Dose Normalized Cmax is the maximum observed concentration of drug substance in plasma normalized for different dasatinib dose levels.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 QD Starting Dose
Hide Arm/Group Description:

Stratum 1 (Ph+ CP-CML): Participants with imatinib-resistant Ph+ CML in CP; Stratum 2/3 (PH+ ALL OR AP/BP-CML): Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in AP, or in MBP, or in LBP; or relapsed or refractory Ph+ ALL after imatinib use; or second or subsequent relapse of Ph+ AML; Stratum 4 (PH- ALL/AML): Participants with second or subsequent relapse of Ph- ALL or Ph- AML.

Strata 1, 2/3, and 4: 60 mg/m^2 starting dose; 80 mg/m^2 escalated/dose level 2; Stratum 4: 100 mg/m^2 escalated/dose level 3 and 120 mg/m^2 escalated/dose level 4. QD, as long as clinical benefit was observed.

Overall Number of Participants Analyzed 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg/m^2
Infants and Toddlers (age<2 years old; n=2)
1.0
(15.2%)
Children (age>=2 and <12 years old; n=43)
1.9
(79.9%)
Adolescents (age>=12 and <18 years old; n=28)
1.0
(69.7%)
Above 18 Years (n=1)
0.9 [1] 
(NA%)
Total (n=74)
1.5
(86.9%)
[1]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
32.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-T] is the area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, normalized by dasatinib dose level.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 QD Starting Dose
Hide Arm/Group Description:

Stratum 1 (Ph+ CP-CML): Participants with imatinib-resistant Ph+ CML in CP; Stratum 2/3 (PH+ ALL OR AP/BP-CML): Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in AP, or in MBP, or in LBP; or relapsed or refractory Ph+ ALL after imatinib use; or second or subsequent relapse of Ph+ AML; Stratum 4 (PH- ALL/AML): Participants with second or subsequent relapse of Ph- ALL or Ph- AML.

Strata 1, 2/3, and 4: 60 mg/m^2 starting dose; 80 mg/m^2 escalated/dose level 2; Stratum 4: 100 mg/m^2 escalated/dose level 3 and 120 mg/m^2 escalated/dose level 4. QD, as long as clinical benefit was observed.

Overall Number of Participants Analyzed 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL/mg/m^2
Infants and Toddlers (age<2 years old; n=2)
2.8
(4.6%)
Children (age>=2 and <12 years old; n=40)
6.1
(95.7%)
Adolescents (age>=12 and <18 years old; n=28)
3.8
(66.8%)
Above 18 Years (n=1)
2.2 [1] 
(NA%)
Total (n=71)
4.9
(98.1%)
[1]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
33.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Dose Normalized Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) by Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time, normalized by dasatinib dose level.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 QD Starting Dose
Hide Arm/Group Description:

Stratum 1 (Ph+ CP-CML): Participants with imatinib-resistant Ph+ CML in CP; Stratum 2/3 (PH+ ALL OR AP/BP-CML): Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in AP, or in MBP, or in LBP; or relapsed or refractory Ph+ ALL after imatinib use; or second or subsequent relapse of Ph+ AML; Stratum 4 (PH- ALL/AML): Participants with second or subsequent relapse of Ph- ALL or Ph- AML.

Strata 1, 2/3, and 4: 60 mg/m^2 starting dose; 80 mg/m^2 escalated/dose level 2; Stratum 4: 100 mg/m^2 escalated/dose level 3 and 120 mg/m^2 escalated/dose level 4. QD, as long as clinical benefit was observed.

Overall Number of Participants Analyzed 53
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL/mg/m^2
Infants and Toddlers (age<2 years old; n=2)
3.2
(17.7%)
Children (age>=2 and <12 years old; n=36)
6.7
(95.0%)
Adolescents (age>=12 and <18 years old; n=22)
4.2
(67.6%)
Above 18 Years (n=1)
2.4 [1] 
(NA%)
Total (n=61)
5.4
(97.1%)
[1]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
34.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 20 25 19 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Infants and Toddlers (age>2yr; n=0; n=0; n=1; n=1)
NA [1] 
(NA%)
NA [1] 
(NA%)
30.6 [2] 
(NA%)
53.8 [2] 
(NA%)
Children (age>=2 & <12yr; n=11; n=16; n=9; n=7)
110.6
(61.8%)
142.5
(80.2%)
111.2
(82.6%)
208.4
(78.5%)
Adolescents (age>=12; n=9; n=8; n=9; n=2)
92.6
(50.6%)
116.5
(73.0%)
235.1
(59.0%)
123.3
(68.3%)
Above 18 years (n=0; n=1; n=0; n=0)
NA [1] 
(NA%)
143.2 [2] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Total
102.1
(58.0%)
133.6
(77.6%)
148.1
(75.0%)
163.9
(87.6%)
[1]
No participants in this age group.
[2]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
35.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 20 25 19 10
Median (Full Range)
Unit of Measure: hour
Infants and Toddlers (age<2yr; n=0; n=0; n=1; n=1)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
0.5
(0.5 to 0.5)
0.5
(0.5 to 0.5)
Children (age>=2 & <12yr; n=11; n=16; n=9; n=7)
1.1
(0.5 to 2.1)
1.5
(0.5 to 3.2)
1.1
(0.6 to 4.1)
1.0
(0.9 to 2.2)
Adolescents (age>=12 & <12yr; n=9; n=8; n=9; n=2)
1.0
(0.5 to 4.0)
1.1
(0.5 to 4.0)
1.0
(0.5 to 6.0)
1.6
(1.0 to 2.1)
Above 18 years (n=0; n=1; n=0; n=0)
NA [1] 
(NA to NA)
0.9
(0.9 to 0.9)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Total
1.0
(0.5 to 4.0)
1.1
(0.5 to 4.0)
1.0
(0.5 to 6.0)
1.0
(0.5 to 2.2)
[1]
No participants in this age group.
36.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-T) is the area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

n=number of PK parameters included.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 19 25 18 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL
Infants and Toddlers (age<2yr; n=0; n=0; n=1; n=1)
NA [1] 
(NA% to NA%)
NA [1] 
(NA%)
100.8 [2] 
(NA%)
134.9 [2] 
(NA%)
Children (age>=2 & <12yr; n=10; n=16; n=8; n=6)
295.0
(63.5%)
490.8
(96.7%)
373.5
(82.0%)
676.7
(99.9%)
Adolescents (age>=12 & <18yr; n=9; n=8; n=9; n=2)
320.8
(59.1%)
488.1
(35.0%)
787.0
(76.2%)
526.1
(56.6%)
Above 18 years (n=0; n=1; n=0; n=0)
NA [1] 
(NA%)
367.2 [2] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Total
307.0
(60.2%)
484.3
(88.9%)
504.1
(89.6%)
534.9
(103.9%)
[1]
No participants in this age group.
[2]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
37.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF]) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(INF) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. n=number of PK parameters included.

Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 18 20 15 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL
Infants and Toddlers (age<2yr; n=0; n=0; n=1; n=1)
0
(0%)
0
(0%)
127.7 [1] 
(NA%)
142.1 [1] 
(NA%)
Children (age>=2 & <12yr; n=10; n=14; n=7; n=5)
313.9
(59.8%)
513.6
(99.2%)
429.1
(76.8%)
817.6
(93.7%)
Adolescents (age>=12 & <18yr; n=8; n=5; n=7; n=2)
305.8
(60.9%)
605.1
(25.3%)
1008.9
(69.4%)
547.8
(58.2%)
Above 18 years (n=0; n=1; n=0; n=0)
0
(0%)
390.0 [1] 
(NA%)
0
(0%)
0
(0%)
Total
310.3
(58.6%)
527.8
(90.4%)
589.8
(86.2%)
594.4
(101.5%)
[1]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
38.Secondary Outcome
Title Dasatinib Plasma Pharmacokinetic Parameter: Terminal Half-life (T 1/2) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. n=number of PK parameters included.

Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 18 20 15 8
Mean (Standard Deviation)
Unit of Measure: hour
Infants and Toddlers (age<2yr; n=0; n=0; n=1; n=1) NA [1]   (NA) NA [1]   (NA) 2.5 [2]   (NA) 1.8 [2]   (NA)
Children (age>=2 & <12yr; n=10; n=14; n=7; n=5) 2.4  (1.0) 3.9  (1.9) 4.6  (3.5) 3.2  (1.9)
Adolescents (age>=12 & <18yr; n=8; n=5; n=7; n=2) 3.7  (1.6) 5.1  (0.5) 4.5  (2.5) 3.5  (2.9)
Above 18 years (n=0; n=1; n=0; n=0) NA [1]   (NA) 7.3 [2]   (NA) NA [1]   (NA) NA [1]   (NA)
Total 3.0  (1.4) 4.4  (1.8) 4.4  (2.9) 3.1  (1.9)
[1]
No participants in this age group.
[2]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
39.Secondary Outcome
Title Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic Parameter: Observed Maximum Plasma Concentration (Cmax) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants with plasma samples available. n=number of PK parameters included. Each participant could have 1, 2, or 3 plasma PK profiles sampled, depending on the number of times the dose of dasatinib was escalated.
Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 18 25 16 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Infants and Toddlers (age<2yr; n=0; n=0; n=0; n=1)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
1.2 [2] 
(NA%)
Children (age>=2 & <12yr; n=10; n=16; n=7; n=7)
3.6
(46.4%)
3.4
(82.0%)
6.0
(69.3%)
4.8
(65.3%)
Adolescents (age>=12 & <18yr; n=8; n=8; n=9; n=2)
3.1
(40.3%)
3.6
(56.7%)
6.9
(75.0%)
4.3
(77.9%)
Above 18 years (n=0; n=1; n=0; n=0)
NA [1] 
(NA%)
2.2 [2] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Total
3.4
(43.7%)
3.4
(74.4%)
6.5
(72.0%)
4.1
(70.8%)
[1]
No participants in this age group.
[2]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
40.Secondary Outcome
Title Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic (PK) Parameter: Time to Achieve the Observed Maximum Plasma Concentration (Tmax) By Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. n=number of PK parameters included.

Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 18 25 16 10
Median (Full Range)
Unit of Measure: hour
Infants and Toddlers (age<2yr; n=0; n=0; n=0; n=1)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
0.9
(0.9 to 0.9)
Children (age>=2 & <12yr; n=10; n=16; n=7; n=7)
2.0
(1.0 to 4.5)
2.0
(0.5 to 6.0)
2.1
(1.0 to 4.1)
2.0
(1.0 to 2.2)
Adolescents (age>=12 & <18yr ; n=8; n=8; n=9; n=2)
2.0
(1.0 to 4.0)
2.0
(1.0 to 4.0)
2.0
(1.0 to 8.1)
2.1
(2.0 to 2.1)
Above 18 years (n=0; n=1; n=0; n=0)
NA [1] 
(NA to NA)
0.9
(0.9 to 0.9)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
Total
2.0
(1.0 to 4.5)
2.0
(0.5 to 6.0)
2.0
(1.0 to 8.1)
2.0
(0.9 to 2.2)
[1]
No participants in this age group.
41.Secondary Outcome
Title Dasatinib Metabolite (BMS-582691) Plasma Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-T]) by Dose Level and Age Group
Hide Description PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-T) is the area under the plasma concentration-time curve from time zero to time of last quantifiable concentration.
Time Frame During Week 1 of Course 1, and any course in which dose escalation was performed (at pre-dose, and at 0.5, 1, 2, 4, 6, 8 and 24 hours).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with plasma samples available. n=number of PK parameters included.

Each participant could have more than 1 plasma profiles sampled, depending on the number of times the dose of dasatinib was escalated.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 13 21 14 9
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng.h/mL
Infants and Toddlers (age<2yr; n=0; n=0; n=0; n=1)
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
1.9 [2] 
(NA%)
Children (age>=2 & <12yr; n=7; n=12; n=5; n=6)
8.8
(50.4%)
16.6
(145.2%)
25.4
(71.1%)
23.6
(102.2%)
Adolescents (age>=12 & <12yr; n=6; n=8; n=9; n=2)
12.3
(38.4%)
13.5
(54.4%)
20.0
(112.3%)
15.8
(105.5%)
Above 18 years (n=0; n=1; n=0; n=0)
NA [2] 
(NA%)
6.6 [2] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
Total
10.3
(44.9%)
14.7
(141.1%)
21.8
(100.1%)
16.3
(110.3%)
[1]
No participants in this age group.
[2]
Due to insufficient number of participants in this age group (only 1 participant), CV% could not be calculated.
42.Secondary Outcome
Title Concentration of Dasatinib in Cerebrospinal Fluid (CSF) by Dose Level and Age Group
Hide Description

Concentration of dasatinib in CSF was assessed only in participants who had lumbar puncture during the treatment.

y=years

Time Frame 4 hours after oral dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

All treated participants with CSF samples available. n=number of PK parameters included.

Each participant could have more than 1 CSF profiles sampled, depending on the number of times the dose of dasatinib was escalated.

Arm/Group Title Dasatinib 60 mg/m^2 Dasatinib 80 mg/m^2 Dasatinib 100 mg/m^2 Dasatinib 120 mg/m^2
Hide Arm/Group Description:
Dasatinib 60 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 80 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 100 mg/m^2 QD, as long as clinical benefit was maintained.

Tablets, Oral; If necessary in participants who could not swallow, tablets were dispersed into 30 cc of 100% fruit juice with no preservatives (minute maid lemonade or orange juice or apple juice).

Dasatinib 120 mg/m^2 QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 4 10 6 1
Mean (Standard Deviation)
Unit of Measure: ng/mL
Children (age>=2 & <12 y; n=3, n=9, n=3, n=1) 1.1  (0.2) 1.5  (0.6) 1.7  (0.4) 3.8 [1]   (NA)
Adolescents (age>=12 & <18 y; n=1; n=1; n=3; n=0) 1.1 [1]   (NA) 1.0 [1]   (NA) 2.6  (0.6) NA [2]   (NA)
Total (Children + Adolescents;n=4; n=10; n=6; n=1) 1.1  (0.1) 1.4  (0.6) 2.1  (0.7) 3.8 [1]   (NA)
[1]
Due to insufficient number of participants in this age group (only 1 participant), standard deviation could not be calculated.
[2]
No participants in this age group.
43.Secondary Outcome
Title Number of Participants With BCR-ABL Mutations at Baseline: Stratum1 Ph+ CP-CML and Stratum 2/3 Ph+ALL or AP/BP-CML
Hide Description BCR-ABL, also referred to as the Philadelphia chromosome, is formed from the fusion of the BCR gene on chromosome 22 with the ABL gene on chromosome 9.
Time Frame At baseline (within 3 weeks before initiation of study therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in strata 1 and 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 17 17
Measure Type: Number
Unit of Measure: participants
L384M 1 0
G250E 1 0
T315I 0 1
Y253H 0 1
Y253F 0 1
No Mutation 15 11
No Data 0 3
44.Secondary Outcome
Title Number of Participants With BCR-ABL Mutations at End-of-Treatment: Stratum1 Ph+ CP-CML and Stratum2/3 Ph+ ALL or AP/BP-CML
Hide Description BCR-ABL = These are fused genes found in participants with this type of leukemia.
Time Frame At EOT (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in strata 1 and 2/3: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Overall Number of Participants Analyzed 17 17
Measure Type: Number
Unit of Measure: participants
T315I 0 4
No Mutation 8 9
No Data 9 4
45.Secondary Outcome
Title Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at Baseline
Hide Description FLT3 and KIT = These are fused genes found in participants with this type of leukemia.
Time Frame At baseline (within 3 weeks before initiation of study therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 4: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
FLT3 Absent 20
FLT3 Present 1
FLT3 No Data 3
KIT Absent 21
KIT Present 0
KIT No Data 3
46.Secondary Outcome
Title Number of Participants With FLT3 and KIT Mutations in Stratum4 Ph- ALL/AML at End-Of-Treatment
Hide Description FLT3 and KIT = These are fused genes found in participants with this type of leukemia.
Time Frame At EOT (Median duration of therapy in months: Stratum 4=1.14 [Range: 0.03-3.38])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants in stratum 4: Participants who received at least 1 dose of study therapy.
Arm/Group Title Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:
Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 24
Measure Type: Number
Unit of Measure: participants
FLT3 Absent 6
FLT3 Present 0
FLT3 No Data 18
KIT Absent 6
KIT Present 0
KIT No Data 18
47.Other Pre-specified Outcome
Title Number of Participants With Hematologic Toxicity at Baseline by NCI CTCAE Version 3.0
Hide Description

GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. White Blood Cell (WBC):GR1=<LLN-3.0*10^9/L; GR2=<3.0-2.0*10^9/L; GR3=<2.0-1.0*10^9/L; GR4=<1.0*10^9/L. Absolute Neutrophil Count (ANC): GR1=<LLN-1.5*10^9 /L; GR2=<1.5-1.0*10^9/L; GR3=<1.0-0.5*10^9/L; GR4=<0.5*10^9/L. Hemoglobin: GR1=<LLN-10.0g/dL; GR2=<10.0-8.0g/dL; GR3=<8.0-6.5g/dL; GR4=<6.5g/dL. Platelets: GR1=<LLN-75.0*10^9/L; GR2=<75.0-50.0*10^9/L; GR3=<50.0-25.0*10^9/L; GR4=<25.0*10^9/L.

LLN=lower limit of normal.

Time Frame At baseline (within 1 week before initiation of study therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 17 17 24
Measure Type: Number
Unit of Measure: participants
WBC GR1 1 2 3
WBC GR2 0 2 2
WBC GR3 0 0 6
WBC GR4 0 1 4
ANC GR1 1 2 3
ANC GR2 1 1 0
ANC GR3 0 2 3
ANC GR4 0 2 13
Platelet GR1 1 5 5
Platelet GR2 0 2 3
Platelet GR3 0 3 8
Platelet GR4 0 2 6
Hemoglobin GR1 7 7 7
Hemoglobin GR2 1 7 7
Hemoglobin GR3 0 1 3
Hemoglobin GR4 0 0 0
48.Other Pre-specified Outcome
Title Number of Participants With Serum Chemistry Abnormalities (Liver and Renal Function) at Baseline by NCI CTCAE Version 3.0
Hide Description

GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Aspartate aminotransferase (AST) and alanine aminotransferase(ALT): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin:GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN.

ULN=upper limit of normal.

Time Frame At baseline (within 1 week before initiation of study therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 17 17 24
Measure Type: Number
Unit of Measure: participants
AST GR1 1 3 8
AST GR2 0 2 1
AST GR3 0 1 0
AST GR4 0 0 0
AST GR Not Reported 1 3 2
High ALT GR1 2 6 6
High ALT GR2 0 2 5
High ALT GR3 0 0 0
High ALT GR4 0 0 0
High ALT GR Not Reported 0 0 0
High Total Bilirubin GR1 3 0 1
High Total Bilirubin GR2 0 1 0
High Total Bilirubin GR3 0 0 0
High Total Bilirubin G4 0 0 0
High Total Bilirubin GR Not Reported 0 0 1
High Serum Creatinine GR1 2 0 4
High Serum Creatinine GR2 0 1 0
High Serum Creatinine GR3 0 0 0
High Serum Creatinine GR4 0 0 0
High Serum Creatinine GR Not Reported 0 0 1
49.Other Pre-specified Outcome
Title Number of Participants With Serum Chemistry Abnormalities (Calcium, Magnesium, and Phosphate) at Baseline by NCI CTCAE Version 3.0
Hide Description GR1=Mild; GR2=Moderate; GR3=Severe; GR4=Life-threatening or disabling. Normal ranges provided by local laboratory and may also vary from site to site. Low calcium: GR1=<LLN–8.0 mg/dL, GR2=<8.0–7.0 mg/dL, GR3=<7.0–6.0 mg/dL, GR4=<6.0 mg/dL; Low magnesium: GR1=<LLN–1.2 mg/dL, GR2=<1.2–0.9 mg/dL, GR3=<0.9–0.7 mg/dL, GR4=<0.7 mg/dL; Low phosphate: GR1=<LLN – 2.5 mg/dL, GR2=<2.5 – 2.0 mg/dL, GR3=<2.0 – 1.0 mg/dL, GR4=<1.0 mg/dL.
Time Frame At baseline (within 1 week before initiation of study therapy)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All treated participants: Participants who received at least one dose of study therapy.
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description:

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
Overall Number of Participants Analyzed 17 17 24
Measure Type: Number
Unit of Measure: participants
Low Calcium GR1 0 0 1
Low Calcium GR2 0 0 0
Low Calcium GR3 0 0 0
Low Calcium GR4 0 0 0
Low Calcium GR Not Reported 0 0 2
Low Magnesium GR1 0 6 0
Low Magnesium GR2 0 0 0
Low Magnesium GR3 0 0 0
Low Magnesium GR4 0 0 0
Low Magnesium GR Not Reported 0 0 2
Low Phosphate GR1 0 1 0
Low Phosphate GR2 0 0 0
Low Phosphate GR3 0 1 0
Low Phosphate GR4 0 0 0
Low Phosphate GR Not Reported 2 0 2
Time Frame From the date of first dose until at least 30 days after the last dose of study drug (Median duration of therapy in months: Stratum 1=24.11 [Range: 2.27-50.63]; Stratum 2/3=3.02 [Range: 0.53-37.72]; Stratum 4=1.14 [Range: 0.03-3.38]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Hide Arm/Group Description

Participants with imatinib-resistant Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

Starting Dose Level of 60 mg/m^2; Escalated/Dose Level 2 of 80 mg/m^2. Once daily (QD), as long as clinical benefit was maintained.

Participants with imatinib-resistant or imatinib-intolerant Ph+ CML in accelerated phase (AP), or in myeloid blast phase (MBP), or in lymphoid blast phase (LBP); or relapsed or refractory Ph+ acute lymphoblastic leukemia (ALL) after imatinib use; or second or subsequent relapse of Ph+ acute myeloid leukemia (AML).

Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2. QD, as long as clinical benefit was maintained.

Participants with second or subsequent relapse of Ph- ALL or Ph- AML. Starting Dose Level of 60 mg/m^2; Escalated/Dose level 2 of 80 mg/m^2, Escalated/Dose level 3 of 100 mg/m^2, and Escalated/Dose level 4 of 120 mg/m^2. QD, as long as clinical benefit was maintained.
All-Cause Mortality
Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/17 (35.29%)   14/17 (82.35%)   22/24 (91.67%) 
Blood and lymphatic system disorders       
Febrile neutropenia  1  0/17 (0.00%)  3/17 (17.65%)  5/24 (20.83%) 
Thrombocytopenia  1  0/17 (0.00%)  2/17 (11.76%)  1/24 (4.17%) 
Cardiac disorders       
Palpitations  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Lower gastrointestinal haemorrhage  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Ileus  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Nausea  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Upper gastrointestinal haemorrhage  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Ascites  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Caecitis  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Enterocolitis  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Pancreatitis  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Vomiting  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Stomatitis  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
General disorders       
Pain  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Performance status decreased  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Thrombosis in device  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Pyrexia  1  1/17 (5.88%)  3/17 (17.65%)  4/24 (16.67%) 
Multi-organ failure  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Immune system disorders       
Graft versus host disease  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Anaphylactic shock  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Infections and infestations       
Cellulitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Device related infection  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Herpes zoster  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Bronchitis  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Gastroenteritis  1  1/17 (5.88%)  0/17 (0.00%)  1/24 (4.17%) 
Infection  1  1/17 (5.88%)  0/17 (0.00%)  2/24 (8.33%) 
Anal infection  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Escherichia sepsis  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Febrile infection  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Pneumonia  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Sepsis  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Septic shock  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Investigations       
Ammonia increased  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Hepatic enzyme increased  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Metabolism and nutrition disorders       
Hypomagnesaemia  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Tumour lysis syndrome  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Decreased appetite  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Hypocalcaemia  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Bone pain  1  1/17 (5.88%)  0/17 (0.00%)  1/24 (4.17%) 
Arthralgia  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Acute myeloid leukaemia  1  0/17 (0.00%)  0/17 (0.00%)  7/24 (29.17%) 
Acute leukaemia  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Acute lymphocytic leukaemia  1  0/17 (0.00%)  1/17 (5.88%)  1/24 (4.17%) 
Nervous system disorders       
Facial nerve disorder  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Syncope  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Coma  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Renal and urinary disorders       
Renal failure  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Respiratory, thoracic and mediastinal disorders       
Pneumonitis  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Pleural effusion  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Respiratory failure  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Skin and subcutaneous tissue disorders       
Exfoliative rash  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Rash  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Urticaria  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Rash macular  1  0/17 (0.00%)  0/17 (0.00%)  1/24 (4.17%) 
Vascular disorders       
Hypertension  1  0/17 (0.00%)  1/17 (5.88%)  0/24 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 14_0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Stratum1 Ph+ CP-CML; Dasatinib 60 mg/m^2 Starting Dose Stratum2/3 Ph+ALL or AP/BP-CML;Dasatinib60mg/m^2 Starting Dose Stratum4 Ph- ALL/AML; Dasatinib 60 mg/m^2 Starting Dose
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   16/17 (94.12%)   16/17 (94.12%)   24/24 (100.00%) 
Blood and lymphatic system disorders       
Neutropenia  1  1/17 (5.88%)  1/17 (5.88%)  0/24 (0.00%) 
Pancytopenia  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Splenomegaly  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Thrombocytopenia  1  1/17 (5.88%)  3/17 (17.65%)  3/24 (12.50%) 
Cardiac disorders       
Palpitations  1  3/17 (17.65%)  1/17 (5.88%)  0/24 (0.00%) 
Ear and labyrinth disorders       
Ear discomfort  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Middle ear effusion  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Ear pain  1  2/17 (11.76%)  3/17 (17.65%)  0/24 (0.00%) 
Eye disorders       
Dry eye  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Erythema of eyelid  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Dacryoadenitis acquired  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Eye discharge  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Periorbital oedema  1  1/17 (5.88%)  0/17 (0.00%)  1/24 (4.17%) 
Eye pain  1  1/17 (5.88%)  2/17 (11.76%)  0/24 (0.00%) 
Conjunctivitis  1  2/17 (11.76%)  1/17 (5.88%)  0/24 (0.00%) 
Eye pruritus  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Eyelid oedema  1  1/17 (5.88%)  1/17 (5.88%)  2/24 (8.33%) 
Chalazion  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Orbital oedema  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Gastrointestinal disorders       
Abdominal pain  1  7/17 (41.18%)  2/17 (11.76%)  3/24 (12.50%) 
Mouth ulceration  1  3/17 (17.65%)  0/17 (0.00%)  0/24 (0.00%) 
Colitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Constipation  1  1/17 (5.88%)  0/17 (0.00%)  1/24 (4.17%) 
Nausea  1  6/17 (35.29%)  6/17 (35.29%)  13/24 (54.17%) 
Gingival bleeding  1  0/17 (0.00%)  1/17 (5.88%)  2/24 (8.33%) 
Abdominal discomfort  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Aphthous stomatitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Diarrhoea  1  10/17 (58.82%)  7/17 (41.18%)  6/24 (25.00%) 
Dyspepsia  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Tongue disorder  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Tooth loss  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Vomiting  1  9/17 (52.94%)  7/17 (41.18%)  11/24 (45.83%) 
Abdominal pain upper  1  3/17 (17.65%)  1/17 (5.88%)  0/24 (0.00%) 
Periodontal disease  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Toothache  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
General disorders       
Catheter site erythema  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Influenza like illness  1  2/17 (11.76%)  2/17 (11.76%)  1/24 (4.17%) 
Pain  1  1/17 (5.88%)  3/17 (17.65%)  0/24 (0.00%) 
Fatigue  1  5/17 (29.41%)  4/17 (23.53%)  4/24 (16.67%) 
Asthenia  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Chest pain  1  2/17 (11.76%)  2/17 (11.76%)  0/24 (0.00%) 
Localised oedema  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Catheter site haemorrhage  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Injection site reaction  1  1/17 (5.88%)  1/17 (5.88%)  0/24 (0.00%) 
Malaise  1  3/17 (17.65%)  0/17 (0.00%)  0/24 (0.00%) 
Pyrexia  1  5/17 (29.41%)  8/17 (47.06%)  8/24 (33.33%) 
Mucosal inflammation  1  1/17 (5.88%)  1/17 (5.88%)  0/24 (0.00%) 
Oedema peripheral  1  3/17 (17.65%)  1/17 (5.88%)  0/24 (0.00%) 
Hepatobiliary disorders       
Hepatomegaly  1  0/17 (0.00%)  0/17 (0.00%)  2/24 (8.33%) 
Hyperbilirubinaemia  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Immune system disorders       
Seasonal allergy  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Infections and infestations       
Cystitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Device related infection  1  0/17 (0.00%)  1/17 (5.88%)  2/24 (8.33%) 
Herpes zoster  1  0/17 (0.00%)  2/17 (11.76%)  0/24 (0.00%) 
Oral herpes  1  1/17 (5.88%)  2/17 (11.76%)  1/24 (4.17%) 
Pharyngitis  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Viral rhinitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Gastrointestinal infection  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Infection  1  2/17 (11.76%)  1/17 (5.88%)  2/24 (8.33%) 
Nasopharyngitis  1  8/17 (47.06%)  2/17 (11.76%)  0/24 (0.00%) 
Urinary tract infection  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Viral infection  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Conjunctivitis bacterial  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Skin infection  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Lice infestation  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Eye infection  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Otitis media  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Sinusitis  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Rhinitis  1  3/17 (17.65%)  1/17 (5.88%)  1/24 (4.17%) 
Upper respiratory tract infection  1  3/17 (17.65%)  3/17 (17.65%)  0/24 (0.00%) 
Varicella  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Injury, poisoning and procedural complications       
Sunburn  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Excoriation  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Mouth injury  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Wound  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Head injury  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Clavicle fracture  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Joint injury  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Post-traumatic pain  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Arthropod bite  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Contusion  1  2/17 (11.76%)  3/17 (17.65%)  0/24 (0.00%) 
Joint sprain  1  2/17 (11.76%)  0/17 (0.00%)  0/24 (0.00%) 
Investigations       
Thermometry abnormal  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Heart rate increased  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Weight decreased  1  0/17 (0.00%)  0/17 (0.00%)  4/24 (16.67%) 
Weight increased  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
White blood cell count  1  0/17 (0.00%)  1/17 (5.88%)  1/24 (4.17%) 
Haemoglobin decreased  1  0/17 (0.00%)  2/17 (11.76%)  2/24 (8.33%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/17 (5.88%)  2/17 (11.76%)  0/24 (0.00%) 
Hypokalaemia  1  0/17 (0.00%)  0/17 (0.00%)  3/24 (12.50%) 
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  2/17 (11.76%)  1/17 (5.88%)  2/24 (8.33%) 
Neck pain  1  1/17 (5.88%)  1/17 (5.88%)  0/24 (0.00%) 
Epiphyses delayed fusion  1  1/17 (5.88%)  0/17 (0.00%)  0/24 (0.00%) 
Pain in extremity  1  8/17 (47.06%)  5/17 (29.41%)  2/24 (8.33%) 
Bone pain  1  1/17 (5.88%)  1/17 (5.88%)  4/24 (16.67%) 
Myalgia  1  4/17 (23.53%)  1/17 (5.88%)  1/24 (4.17%) 
Musculoskeletal chest pain  1  1/17 (5.88%)  1/17 (5.88%)  0/24 (0.00%) 
Osteonecrosis  1