Trial Outcomes & Findings for Dasatinib (BMS-354825) in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate (NCT NCT00101816)
NCT ID: NCT00101816
Last Updated: 2010-08-10
Results Overview
MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts + promyelocytes in bone marrow and \<30% blasts + promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
124 participants
Primary outcome timeframe
Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatment
Results posted on
2010-08-10
Participant Flow
A total of 124 participants were enrolled in this study; 15 were never treated (11 participants did not meet inclusion criteria; 3 participants died; 1 participant failed screening).
Participant milestones
| Measure |
Imatinib-intolerant
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
99
|
|
Overall Study
COMPLETED
|
10
|
99
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dasatinib (BMS-354825) in Subjects With Myeloid Blast Phase Chronic Myeloid Leukemia Resistant to or Intolerant of Imatinib Mesylate
Baseline characteristics by cohort
| Measure |
Imatinib-intolerant
n=10 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=109 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Between 21 and 45 years
|
1 participants
n=99 Participants
|
35 participants
n=107 Participants
|
36 participants
n=206 Participants
|
|
Age, Customized
Between 46 and 65 years
|
7 participants
n=99 Participants
|
46 participants
n=107 Participants
|
53 participants
n=206 Participants
|
|
Age, Customized
Between 66 and 75 years
|
1 participants
n=99 Participants
|
18 participants
n=107 Participants
|
19 participants
n=206 Participants
|
|
Age, Customized
>75 years
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Age Continuous
|
60.5 years
STANDARD_DEVIATION 10.9 • n=99 Participants
|
50.4 years
STANDARD_DEVIATION 14.0 • n=107 Participants
|
51.4 years
STANDARD_DEVIATION 14.0 • n=206 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=99 Participants
|
60 Participants
n=107 Participants
|
63 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
46 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
18 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=99 Participants
|
13 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White
|
10 Participants
n=99 Participants
|
67 Participants
n=107 Participants
|
77 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=0
|
1 Participants
n=99 Participants
|
21 Participants
n=107 Participants
|
22 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=1
|
6 Participants
n=99 Participants
|
39 Participants
n=107 Participants
|
45 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=2
|
2 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=3
|
0 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=4
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Score=5
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS)
Not Reported
|
1 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
5 Participants
n=206 Participants
|
|
Functional Assessment of Cancer Therapy-General (FACT-G)
Total FACT-G
|
65.6 units on a scale
STANDARD_DEVIATION 7.1 • n=99 Participants
|
69.2 units on a scale
STANDARD_DEVIATION 16.0 • n=107 Participants
|
68.9 units on a scale
STANDARD_DEVIATION 15.4 • n=206 Participants
|
|
Functional Assessment of Cancer Therapy-General (FACT-G)
Physical Well Being
|
17.2 units on a scale
STANDARD_DEVIATION 3.8 • n=99 Participants
|
16.4 units on a scale
STANDARD_DEVIATION 6.3 • n=107 Participants
|
16.5 units on a scale
STANDARD_DEVIATION 6.1 • n=206 Participants
|
|
Functional Assessment of Cancer Therapy-General (FACT-G)
Social/Family Well-Being
|
20.1 units on a scale
STANDARD_DEVIATION 23.6 • n=99 Participants
|
22.1 units on a scale
STANDARD_DEVIATION 4.7 • n=107 Participants
|
21.9 units on a scale
STANDARD_DEVIATION 4.7 • n=206 Participants
|
|
Functional Assessment of Cancer Therapy-General (FACT-G)
Emotional Well-Being
|
15.3 units on a scale
STANDARD_DEVIATION 2.1 • n=99 Participants
|
16.8 units on a scale
STANDARD_DEVIATION 5.3 • n=107 Participants
|
16.7 units on a scale
STANDARD_DEVIATION 5.2 • n=206 Participants
|
|
Functional Assessment of Cancer Therapy-General (FACT-G)
Functional Well-Being
|
13.0 units on a scale
STANDARD_DEVIATION 4.5 • n=99 Participants
|
13.9 units on a scale
STANDARD_DEVIATION 5.9 • n=107 Participants
|
13.8 units on a scale
STANDARD_DEVIATION 5.7 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatmentPopulation: All treated subjects
MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. OHR=best confirmed response of MaHR or minor HR (MiHR). MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts + promyelocytes in bone marrow and \<30% blasts + promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea.
Outcome measures
| Measure |
Imatinib-intolerant
n=10 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=109 Participants
|
|---|---|---|---|
|
Major and Overall Hematologic Response (MaHR and OHR)
MaHR
|
2 Participants
|
34 Participants
|
36 Participants
|
|
Major and Overall Hematologic Response (MaHR and OHR)
OHR
|
4 Participants
|
50 Participants
|
54 Participants
|
SECONDARY outcome
Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatmentPopulation: Participants who achieved MaHR
MaHR=best confirmed response of CHR or NEL. CHR=white blood cells ≤ institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; \<5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤ iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; \<5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement; at least 1 of the following: ANC ≥500/mm3 \& \<1000/mm3; platelets ≥20,000/mm3 \& \<100,000/mm3.
Outcome measures
| Measure |
Imatinib-intolerant
n=36 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Median Duration of Major Hematologic Response (MaHR)
|
22.4 months
Interval 1.6 to 27.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatmentPopulation: Participants who achieved OHR
OHR=best confirmed response of MaHR or MiHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1. Maintaining a response was defined as no 2 consecutive records of non-response (ie, a single record of non-response between 2 assessments of response was not considered a loss of response).
Outcome measures
| Measure |
Imatinib-intolerant
n=54 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Median Duration of Overall Hematologic Response (OHR)
|
14.7 months
Interval 10.0 to 22.6
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycle 1 and 2; After every 2nd cycle during Cycles 3+; at end of treatmentPopulation: Participants who achieved OHR and MaHR
Median time from first dosing to date of OHR and/or MaHR in subjects who achieved OHR and MaHR. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Criteria for MaHR are specified in Outcome Measure 2. Criteria for MiHR are specified in Outcome Measure 1.
Outcome measures
| Measure |
Imatinib-intolerant
n=36 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=54 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Time to MaHR and OHR
|
63.5 days
Interval 40.0 to 85.0
|
30.0 days
Interval 29.0 to 37.0
|
—
|
SECONDARY outcome
Timeframe: Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatmentPopulation: All treated subjects
Best confirmed cytogenetic response. Determination of cytogenetic response is based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).
Outcome measures
| Measure |
Imatinib-intolerant
n=10 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=109 Participants
|
|---|---|---|---|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Unable to Determine
|
4 Participants
|
22 Participants
|
26 Participants
|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Complete (0% Ph+ metaphases)
|
2 Participants
|
27 Participants
|
29 Participants
|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Partial (>0% to 35% Ph+ metaphases)
|
0 Participants
|
8 Participants
|
8 Participants
|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Minor (>35% to 65% Ph+ metaphases)
|
0 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
Minimal (>65% to 95% Ph+ metaphases)
|
0 Participants
|
11 Participants
|
11 Participants
|
|
Number of Participants With Complete, Partial, Minor, Minimal, or No Cytogenetic Response
No Response (>95% to 100% Ph+ metaphases)
|
4 Participants
|
28 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during Cycles 1 and 2; After every 2nd cycle for Cycles 3+; at end of treatmentPopulation: All treated subjects
Best confirmed hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for complete hematologic response (CHR) or No Evidence of Leukemia (NEL) are specified in Outcome Measure 2. Criteria for minor hematologic response (MiHR) are specified in Outcome Measure 1.
Outcome measures
| Measure |
Imatinib-intolerant
n=10 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=109 Participants
|
|---|---|---|---|
|
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
Complete
|
2 Participants
|
26 Participants
|
28 Participants
|
|
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
No evidence of leukemia
|
0 Participants
|
8 Participants
|
8 Participants
|
|
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
Minor
|
2 Participants
|
16 Participants
|
18 Participants
|
|
Number of Participants With CHR or NEL, MiHR, or no Hematologic Response
No response
|
6 Participants
|
49 Participants
|
55 Participants
|
SECONDARY outcome
Timeframe: Baseline, every 12 weeks, and at time of Complete Cytogenetic Response (CCyR) for quantitative Polyermase Chain Reaction (qPCR) analysisPopulation: treated participants with or without CCyR who were assessed for major molecular response
Number of participants who achieved an MMR at any time during the treatment period. MMR was calulated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).
Outcome measures
| Measure |
Imatinib-intolerant
n=3 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=45 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=48 Participants
|
|---|---|---|---|
|
Number of Participants Achieving Major Molecular Response (MMR)
MMR in Assessed Subjects with CCyR (n=2; n=17)
|
2 participants
|
11 participants
|
13 participants
|
|
Number of Participants Achieving Major Molecular Response (MMR)
MMR in Assessed Subjects without CCyR (n=1; n=28)
|
0 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: baseline, at time of disease progressionPopulation: All subjects with baseline mutation data; n=the number of participants with the specified mutation. Baseline mutation data were reported for 103 of the 109 subjects (10/10 imatinib-intolerant and 93/99 imatinib-resistant). At baseline, 39 (42%) imatinib-resistant subjects and 3 imatinib-intolerant subject had imatinib-resistant mutations
MaHR and MCyR in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). Criteria for MaHR are specified in Outcome Measure 2. MCyR=rate of complete cytogenetic responses + the rate of partial cytogenetic responses, as defined in Outcome Measure 5. BCR-ABL=the fused gene found in subjects with this type of CML. This table contains those mutations observed in at least 3 participants. The categories "1 IRM w/2-4-fold increase in resistance" and "≥1 IRM w/≥5-fold increase in resistance" refer to increase in resistance to imatinib.
Outcome measures
| Measure |
Imatinib-intolerant
n=103 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=103 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
Participants with IRM (n=42)
|
31 Percentage of Participants
|
29 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
≥1 IRM in P-loop (n=19)
|
26 Percentage of Participants
|
26 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
≥1 IRM in activation loop (n=8)
|
38 Percentage of Participants
|
13 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
≥1 IRM in other location (n=17)
|
29 Percentage of Participants
|
35 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
≥1 IRM w/2-4-fold increase in resistance (n=4)
|
75 Percentage of Participants
|
50 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
≥1 IRM w/≥5-fold increase in resistance (n=28)
|
25 Percentage of Participants
|
25 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [M244V] at baseline (n=3)
|
33 Percentage of Participants
|
33 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [G250E] at baseline (n=7)
|
29 Percentage of Participants
|
14 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [Y253H] at baseline (n=6)
|
50 Percentage of Participants
|
50 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [E255K/V] at baseline (n=5)
|
0 Percentage of Participants
|
20 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [T315I] at baseline (n=5)
|
0 Percentage of Participants
|
20 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [M351T/V] at baseline (n=3)
|
67 Percentage of Participants
|
67 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [F359I/V] at baseline (n=3)
|
0 Percentage of Participants
|
0 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [H396R] at baseline (n=4)
|
25 Percentage of Participants
|
0 Percentage of Participants
|
—
|
|
MaHR and Major Cytogenetic Response (MCyR) Among Participants With Baseline BCR-ABL Point Mutations
SBAM [F486S] at baseline (n=4)
|
0 Percentage of Participants
|
0 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: Baseline, Every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-upPopulation: Number of participants with FACT-G assessments at baseline and at least one assessment during treatment
Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, \& functional well-being (PWB, SWB, EWB, FWB). Score range: 0-108; higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, \& SWB score change of 2 or more=minimal clinical important change.
Outcome measures
| Measure |
Imatinib-intolerant
n=7 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=81 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=88 Participants
|
|---|---|---|---|
|
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Total Fact-G
|
5 Participants
|
46 Participants
|
51 Participants
|
|
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Physical Well-Being
|
5 Participants
|
54 Participants
|
59 Participants
|
|
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Social/Family Well-Being
|
4 Participants
|
35 Participants
|
39 Participants
|
|
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Emotional Well-Being
|
4 Participants
|
37 Participants
|
41 Participants
|
|
Minimally Significant Changes From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G)
Functional Well-Being
|
3 Participants
|
42 Participants
|
45 Participants
|
SECONDARY outcome
Timeframe: Continuously throughout study, from pre-treatment visit through end of study (due to death, unacceptable toxicity, treatment failure, etc) and follow-up periodPopulation: All treated subjects
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Outcome measures
| Measure |
Imatinib-intolerant
n=10 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
n=109 Participants
|
|---|---|---|---|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
Death Within 30 Days
|
6 Participants
|
38 Participants
|
44 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
Death
|
6 Participants
|
49 Participants
|
55 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
SAEs
|
7 Participants
|
80 Participants
|
87 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
AEs
|
10 Participants
|
99 Participants
|
109 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
AEs Leading to Discontinuation
|
3 Participants
|
39 Participants
|
42 Participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), AEs Leading to Discontinuation, Drug-Related AEs
Drug-Related AEs
|
9 Participants
|
91 Participants
|
100 Participants
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 and Day 8; parameters for 1 participant on Day 8 was excluded due to unreliable data. Participants with all concentration-time values \< than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Outcome measures
| Measure |
Imatinib-intolerant
n=24 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=19 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib - Maximum Observed Plasma Concentration (Cmax)
|
60.34 ng/mL
Standard Deviation 55.86
|
110.42 ng/mL
Standard Deviation 44.31
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 and Day 8; parameters for 1 participant on Day 8 was excluded due to unreliable data. Participants with all concentration-time values \< than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were \< lower limit of qualtitation were assigned a value of zero.
Outcome measures
| Measure |
Imatinib-intolerant
n=24 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=19 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h or 24 h(AUC[0-T])
|
161.17 ng∙h/mL
Standard Deviation 150.29
|
295.92 ng∙h/mL
Standard Deviation 169.20
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 and Day 8; parameters for 1 participant on Day 8 was excluded due to unreliable data. Participants with all concentration-time values \< than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Outcome measures
| Measure |
Imatinib-intolerant
n=24 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=19 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib - Time to Maximum Observed Plasma Concentration (Tmax)
|
1.79 hours
Standard Deviation 1.45 • Interval 0.47 to 6.0
|
1.22 hours
Standard Deviation 0.97 • Interval 0.25 to 3.0
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 and Day 8; parameters for 1 participant on Day 8 was excluded due to unreliable data. Participants with all concentration-time values \< than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Outcome measures
| Measure |
Imatinib-intolerant
n=23 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=19 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib - Plasma Half-life (T-HALF)
|
3.71 hours
Standard Deviation 1.78
|
4.26 hours
Standard Deviation 2.15
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 \& Day 8; parameters for 1 participant on Day 1 \& 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \<than limit of quantitation were treated as missing for PK analysis. n=participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Outcome measures
| Measure |
Imatinib-intolerant
n=14 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=18 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax)
|
2.44 ng/mL
Standard Deviation 1.32
|
3.87 ng/mL
Standard Deviation 1.67
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 \& Day 8; parameters for 1 participant on Day 1 \& 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \<than limit of quantitation were treated as missing for PK analysis. n=participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.
Outcome measures
| Measure |
Imatinib-intolerant
n=14 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=18 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 h (AUC[0-T])
|
7.08 ng∙h/mL
Standard Deviation 7.80
|
13.81 ng∙h/mL
Standard Deviation 11.96
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 \& Day 8; parameters for 1 participant on Day 1 \& 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \<than limit of quantitation were treated as missing for PK analysis. n=participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.
Outcome measures
| Measure |
Imatinib-intolerant
n=14 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=18 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib's Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax)
|
1.71 hours
Standard Deviation 1.00
|
1.90 hours
Standard Deviation 1.49
|
—
|
SECONDARY outcome
Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.Population: 26 participants had dense PK sampling on Day 1 \& Day 8; parameters for 1 participant on Day 1 \& 1 on Day 8 were excluded due to unreliable data. Participants w/all concentration-time values \<than limit of quantitation were treated as missing for PK analysis. n=participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.
The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.
Outcome measures
| Measure |
Imatinib-intolerant
n=14 Participants
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=18 Participants
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
Total
|
|---|---|---|---|
|
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF)
|
4.95 hours
Standard Deviation 3.93
|
4.38 hours
Standard Deviation 3.97
|
—
|
SECONDARY outcome
Timeframe: Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.Population pharmacokinetic analysis was not done because it is not meaningful for this single study
Outcome measures
Outcome data not reported
Adverse Events
Imatinib-intolerant
Serious events: 7 serious events
Other events: 10 other events
Deaths: 0 deaths
Imatinib-resistant
Serious events: 80 serious events
Other events: 97 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Imatinib-intolerant
n=10 participants at risk
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 participants at risk
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
|---|---|---|
|
Cardiac disorders
NODAL ARRHYTHMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Cardiac disorders
SINUS TACHYCARDIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
0.00%
0/10
|
2.0%
2/99
|
|
Cardiac disorders
MYOCARDIAL ISCHAEMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
ASCITES
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
MELAENA
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
VOMITING
|
10.0%
1/10
|
3.0%
3/99
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/10
|
2.0%
2/99
|
|
Gastrointestinal disorders
STOMATITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
0.00%
0/10
|
2.0%
2/99
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
10.0%
1/10
|
3.0%
3/99
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
NEUTROPENIC COLITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
ABDOMINAL PAIN LOWER
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
LARGE INTESTINAL ULCER
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
10.0%
1/10
|
9.1%
9/99
|
|
Gastrointestinal disorders
LOWER GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/10
|
3.0%
3/99
|
|
Infections and infestations
SEPSIS
|
0.00%
0/10
|
11.1%
11/99
|
|
Infections and infestations
GANGRENE
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
INFECTION
|
0.00%
0/10
|
5.1%
5/99
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.00%
0/10
|
4.0%
4/99
|
|
Cardiac disorders
MYOCARDIAL INFARCTION
|
0.00%
0/10
|
2.0%
2/99
|
|
Cardiac disorders
CONGESTIVE CARDIOMYOPATHY
|
0.00%
0/10
|
1.0%
1/99
|
|
Cardiac disorders
CARDIAC FAILURE CONGESTIVE
|
0.00%
0/10
|
3.0%
3/99
|
|
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION
|
10.0%
1/10
|
0.00%
0/99
|
|
Cardiac disorders
ARRHYTHMIA SUPRAVENTRICULAR
|
0.00%
0/10
|
1.0%
1/99
|
|
Cardiac disorders
LEFT VENTRICULAR DYSFUNCTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Cardiac disorders
SUPRAVENTRICULAR TACHYCARDIA
|
0.00%
0/10
|
2.0%
2/99
|
|
Vascular disorders
FLUSHING
|
0.00%
0/10
|
1.0%
1/99
|
|
Vascular disorders
THROMBOPHLEBITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Hepatobiliary disorders
HEPATOSPLENOMEGALY
|
0.00%
0/10
|
1.0%
1/99
|
|
Hepatobiliary disorders
CHOLECYSTITIS ACUTE
|
0.00%
0/10
|
1.0%
1/99
|
|
Hepatobiliary disorders
CYTOLYTIC HEPATITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Nervous system disorders
APHASIA
|
10.0%
1/10
|
0.00%
0/99
|
|
Nervous system disorders
HEADACHE
|
0.00%
0/10
|
3.0%
3/99
|
|
Nervous system disorders
MYELITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/10
|
1.0%
1/99
|
|
Nervous system disorders
CEREBRAL ISCHAEMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Nervous system disorders
CEREBRAL HAEMORRHAGE
|
0.00%
0/10
|
4.0%
4/99
|
|
Nervous system disorders
MENINGITIS NONINFECTIVE
|
10.0%
1/10
|
1.0%
1/99
|
|
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
|
0.00%
0/10
|
1.0%
1/99
|
|
Nervous system disorders
INTRACRANIAL PRESSURE INCREASED
|
10.0%
1/10
|
0.00%
0/99
|
|
Nervous system disorders
DEPRESSED LEVEL OF CONSCIOUSNESS
|
0.00%
0/10
|
1.0%
1/99
|
|
Gastrointestinal disorders
NAUSEA
|
10.0%
1/10
|
3.0%
3/99
|
|
Investigations
TROPONIN I
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
HAEMOGLOBIN
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
HAEMOGLOBIN DECREASED
|
10.0%
1/10
|
1.0%
1/99
|
|
Investigations
CARDIAC ENZYMES INCREASED
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
BLAST CELL COUNT INCREASED
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
GRANULOCYTE COUNT DECREASED
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
PLATELET AGGREGATION ABNORMAL
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
0.00%
0/10
|
1.0%
1/99
|
|
Investigations
ELECTROCARDIOGRAM QT CORRECTED INTERVAL PROLONGED
|
0.00%
0/10
|
2.0%
2/99
|
|
Cardiac disorders
ANGINA UNSTABLE
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
PNEUMONIA
|
10.0%
1/10
|
6.1%
6/99
|
|
Infections and infestations
CELLULITIS
|
0.00%
0/10
|
3.0%
3/99
|
|
Infections and infestations
PHARYNGITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
SEPTIC SHOCK
|
0.00%
0/10
|
2.0%
2/99
|
|
Infections and infestations
BRAIN ABSCESS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
LIVER ABSCESS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
ANAL INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
LUNG INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
PYELONEPHRITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
CATHETER SEPSIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
PERIANAL ABSCESS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
ASCITES INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
LOCALISED INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
DIARRHOEA INFECTIOUS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
NEUTROPENIC INFECTION
|
0.00%
0/10
|
3.0%
3/99
|
|
Infections and infestations
CYTOMEGALOVIRUS COLITIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
URINARY TRACT INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
ENTEROCOLITIS INFECTIOUS
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
CYTOMEGALOVIRUS INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
|
0.00%
0/10
|
1.0%
1/99
|
|
Renal and urinary disorders
HAEMATURIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Renal and urinary disorders
RENAL FAILURE
|
0.00%
0/10
|
3.0%
3/99
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Renal and urinary disorders
RENAL IMPAIRMENT
|
0.00%
0/10
|
1.0%
1/99
|
|
Surgical and medical procedures
INTESTINAL STOMA
|
0.00%
0/10
|
1.0%
1/99
|
|
Surgical and medical procedures
STEM CELL TRANSPLANT
|
0.00%
0/10
|
1.0%
1/99
|
|
Surgical and medical procedures
BONE MARROW TRANSPLANT
|
0.00%
0/10
|
2.0%
2/99
|
|
Metabolism and nutrition disorders
ANOREXIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
0.00%
0/10
|
1.0%
1/99
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Metabolism and nutrition disorders
HYPERCALCAEMIA
|
0.00%
0/10
|
2.0%
2/99
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Metabolism and nutrition disorders
DIABETES MELLITUS
|
0.00%
0/10
|
1.0%
1/99
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/10
|
7.1%
7/99
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
0.00%
0/10
|
4.0%
4/99
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
0.00%
0/10
|
3.0%
3/99
|
|
Blood and lymphatic system disorders
PANCYTOPENIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Blood and lymphatic system disorders
SPLENOMEGALY
|
0.00%
0/10
|
1.0%
1/99
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
20.0%
2/10
|
5.1%
5/99
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
10.0%
1/10
|
10.1%
10/99
|
|
Skin and subcutaneous tissue disorders
RASH
|
0.00%
0/10
|
1.0%
1/99
|
|
Skin and subcutaneous tissue disorders
PURPURA
|
0.00%
0/10
|
2.0%
2/99
|
|
Skin and subcutaneous tissue disorders
PETECHIAE
|
0.00%
0/10
|
2.0%
2/99
|
|
Skin and subcutaneous tissue disorders
DECUBITUS ULCER
|
0.00%
0/10
|
1.0%
1/99
|
|
Skin and subcutaneous tissue disorders
URTICARIA VESICULOSA
|
0.00%
0/10
|
1.0%
1/99
|
|
Skin and subcutaneous tissue disorders
HAEMORRHAGE SUBCUTANEOUS
|
0.00%
0/10
|
1.0%
1/99
|
|
Skin and subcutaneous tissue disorders
ACUTE FEBRILE NEUTROPHILIC DERMATOSIS
|
0.00%
0/10
|
2.0%
2/99
|
|
Injury, poisoning and procedural complications
FRACTURE
|
0.00%
0/10
|
1.0%
1/99
|
|
Injury, poisoning and procedural complications
FEMUR FRACTURE
|
10.0%
1/10
|
0.00%
0/99
|
|
Injury, poisoning and procedural complications
SUBDURAL HAEMATOMA
|
0.00%
0/10
|
3.0%
3/99
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/10
|
1.0%
1/99
|
|
Musculoskeletal and connective tissue disorders
VERTEBRAL COLUMN MASS
|
0.00%
0/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
0.00%
0/10
|
3.0%
3/99
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
10.0%
1/10
|
6.1%
6/99
|
|
Respiratory, thoracic and mediastinal disorders
ORTHOPNOEA
|
0.00%
0/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
CHYLOTHORAX
|
0.00%
0/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
0.00%
0/10
|
6.1%
6/99
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
30.0%
3/10
|
17.2%
17/99
|
|
Respiratory, thoracic and mediastinal disorders
LUNG INFILTRATION
|
0.00%
0/10
|
4.0%
4/99
|
|
Respiratory, thoracic and mediastinal disorders
LUNG CONSOLIDATION
|
0.00%
0/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
10.0%
1/10
|
0.00%
0/99
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
10.0%
1/10
|
2.0%
2/99
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE
|
0.00%
0/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
FATIGUE
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
MALAISE
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
PYREXIA
|
10.0%
1/10
|
17.2%
17/99
|
|
General disorders
ASTHENIA
|
0.00%
0/10
|
2.0%
2/99
|
|
General disorders
CHEST PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
GENERALISED OEDEMA
|
0.00%
0/10
|
2.0%
2/99
|
|
General disorders
DISEASE PROGRESSION
|
0.00%
0/10
|
2.0%
2/99
|
|
General disorders
MUCOSAL INFLAMMATION
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
General disorders
PERFORMANCE STATUS DECREASED
|
0.00%
0/10
|
1.0%
1/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LEUKAEMIA
|
0.00%
0/10
|
1.0%
1/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR PAIN
|
0.00%
0/10
|
1.0%
1/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MYELOFIBROSIS
|
0.00%
0/10
|
1.0%
1/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLAST CELL CRISIS
|
10.0%
1/10
|
2.0%
2/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR LYSIS SYNDROME
|
0.00%
0/10
|
2.0%
2/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLAST CELL PROLIFERATION
|
0.00%
0/10
|
2.0%
2/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
CHRONIC MYELOID LEUKAEMIA
|
10.0%
1/10
|
18.2%
18/99
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BLAST CRISIS IN MYELOGENOUS LEUKAEMIA
|
0.00%
0/10
|
9.1%
9/99
|
Other adverse events
| Measure |
Imatinib-intolerant
n=10 participants at risk
Defined as: i) Toxicity that was considered at least possibly related to imatinib ≤400 mg/day that led to a discontinuation of imatinib therapy ii) Ability to tolerate only \<400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses was not considered imatinib-intolerant. Receiving oral dasatinib at a starting dose of 70 mg twice daily (BID), with dose modifications as necessary for the management of disease progression or toxicity.
|
Imatinib-resistant
n=99 participants at risk
Defined as any of the following: i) Subjects initially diagnosed with chronic phase chronic myeloid leukemia (CML) who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥400 mg/day. ii) Subjects initially diagnosed with accelerated phase CML who progressed to myeloid phase CML while on treatment with a prescribed imatinib dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). iii) Subjects initially diagnosed with myeloid blast phase CML who meet the criteria for myeloid phase blast crisis after at least 4 weeks of treatment prescribed at a dose of ≥600 mg/day (or 400 to \<600 mg/day if subject is intolerant of ≥600 mg/day). Each of these definitions includes subjects who had no response to imatinib (primary resistance) and those who responded and subsequently progressed to myeloid blast phase (acquired resistance). Oral dasatinib 70 mg BID, with dose modifications as necessary to manage disease progression or toxicity.
|
|---|---|---|
|
Eye disorders
DRY EYE
|
10.0%
1/10
|
0.00%
0/99
|
|
Eye disorders
EYE OEDEMA
|
10.0%
1/10
|
1.0%
1/99
|
|
Eye disorders
EYELID OEDEMA
|
10.0%
1/10
|
4.0%
4/99
|
|
Eye disorders
EYE HAEMORRHAGE
|
0.00%
0/10
|
6.1%
6/99
|
|
Eye disorders
RETINAL HAEMORRHAGE
|
10.0%
1/10
|
1.0%
1/99
|
|
Eye disorders
CONJUNCTIVAL HAEMORRHAGE
|
10.0%
1/10
|
8.1%
8/99
|
|
Investigations
CARDIAC MURMUR
|
10.0%
1/10
|
1.0%
1/99
|
|
Investigations
WEIGHT DECREASED
|
50.0%
5/10
|
25.3%
25/99
|
|
Investigations
WEIGHT INCREASED
|
20.0%
2/10
|
21.2%
21/99
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
0.00%
0/10
|
5.1%
5/99
|
|
Investigations
ELECTROCARDIOGRAM QT CORRECTED INTERVAL PROLONGED
|
10.0%
1/10
|
0.00%
0/99
|
|
Cardiac disorders
TACHYCARDIA
|
10.0%
1/10
|
7.1%
7/99
|
|
Cardiac disorders
TACHYARRHYTHMIA
|
10.0%
1/10
|
0.00%
0/99
|
|
Cardiac disorders
ATRIAL FIBRILLATION
|
10.0%
1/10
|
1.0%
1/99
|
|
Cardiac disorders
PERICARDIAL EFFUSION
|
0.00%
0/10
|
7.1%
7/99
|
|
Cardiac disorders
LEFT VENTRICULAR DYSFUNCTION
|
10.0%
1/10
|
0.00%
0/99
|
|
Vascular disorders
HAEMATOMA
|
10.0%
1/10
|
7.1%
7/99
|
|
Vascular disorders
HYPOTENSION
|
10.0%
1/10
|
13.1%
13/99
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/10
|
12.1%
12/99
|
|
Vascular disorders
PERIPHERAL ISCHAEMIA
|
10.0%
1/10
|
0.00%
0/99
|
|
Psychiatric disorders
ANXIETY
|
10.0%
1/10
|
8.1%
8/99
|
|
Psychiatric disorders
INSOMNIA
|
20.0%
2/10
|
13.1%
13/99
|
|
Psychiatric disorders
AGITATION
|
10.0%
1/10
|
0.00%
0/99
|
|
Psychiatric disorders
DEPRESSION
|
0.00%
0/10
|
8.1%
8/99
|
|
Psychiatric disorders
DEPRESSED MOOD
|
20.0%
2/10
|
1.0%
1/99
|
|
Psychiatric disorders
CONFUSIONAL STATE
|
10.0%
1/10
|
1.0%
1/99
|
|
Hepatobiliary disorders
CHOLELITHIASIS
|
10.0%
1/10
|
0.00%
0/99
|
|
Hepatobiliary disorders
HYPERBILIRUBINAEMIA
|
10.0%
1/10
|
0.00%
0/99
|
|
Hepatobiliary disorders
GALLBLADDER ENLARGEMENT
|
10.0%
1/10
|
0.00%
0/99
|
|
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL
|
10.0%
1/10
|
0.00%
0/99
|
|
Immune system disorders
ALLERGY TO ARTHROPOD BITE
|
10.0%
1/10
|
0.00%
0/99
|
|
Nervous system disorders
COMA
|
10.0%
1/10
|
1.0%
1/99
|
|
Nervous system disorders
APHASIA
|
10.0%
1/10
|
2.0%
2/99
|
|
Nervous system disorders
HEADACHE
|
30.0%
3/10
|
31.3%
31/99
|
|
Nervous system disorders
LETHARGY
|
10.0%
1/10
|
1.0%
1/99
|
|
Nervous system disorders
DIZZINESS
|
20.0%
2/10
|
14.1%
14/99
|
|
Nervous system disorders
CONVULSION
|
0.00%
0/10
|
6.1%
6/99
|
|
Nervous system disorders
SOMNOLENCE
|
10.0%
1/10
|
2.0%
2/99
|
|
Nervous system disorders
PARAESTHESIA
|
0.00%
0/10
|
5.1%
5/99
|
|
Nervous system disorders
HYPOAESTHESIA
|
10.0%
1/10
|
2.0%
2/99
|
|
Gastrointestinal disorders
NAUSEA
|
30.0%
3/10
|
34.3%
34/99
|
|
Gastrointestinal disorders
ASCITES
|
0.00%
0/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
VOMITING
|
60.0%
6/10
|
37.4%
37/99
|
|
Gastrointestinal disorders
DIARRHOEA
|
50.0%
5/10
|
60.6%
60/99
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.00%
0/10
|
11.1%
11/99
|
|
Gastrointestinal disorders
GASTRITIS
|
0.00%
0/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
PROCTALGIA
|
10.0%
1/10
|
4.0%
4/99
|
|
Gastrointestinal disorders
STOMATITIS
|
30.0%
3/10
|
14.1%
14/99
|
|
Gastrointestinal disorders
ANAL FISSURE
|
10.0%
1/10
|
0.00%
0/99
|
|
Gastrointestinal disorders
CONSTIPATION
|
20.0%
2/10
|
21.2%
21/99
|
|
Gastrointestinal disorders
HAEMORRHOIDS
|
20.0%
2/10
|
7.1%
7/99
|
|
Gastrointestinal disorders
HAEMATOCHEZIA
|
10.0%
1/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/10
|
22.2%
22/99
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
10.0%
1/10
|
0.00%
0/99
|
|
Gastrointestinal disorders
LIP HAEMORRHAGE
|
10.0%
1/10
|
0.00%
0/99
|
|
Gastrointestinal disorders
GINGIVAL BLEEDING
|
0.00%
0/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
MOUTH HAEMORRHAGE
|
10.0%
1/10
|
6.1%
6/99
|
|
Gastrointestinal disorders
RECTAL HAEMORRHAGE
|
10.0%
1/10
|
4.0%
4/99
|
|
Gastrointestinal disorders
ABDOMINAL DISCOMFORT
|
0.00%
0/10
|
5.1%
5/99
|
|
Gastrointestinal disorders
ABDOMINAL PAIN UPPER
|
20.0%
2/10
|
16.2%
16/99
|
|
Gastrointestinal disorders
GASTROINTESTINAL DISORDER
|
10.0%
1/10
|
0.00%
0/99
|
|
Gastrointestinal disorders
GASTROINTESTINAL HAEMORRHAGE
|
0.00%
0/10
|
10.1%
10/99
|
|
Infections and infestations
RHINITIS
|
10.0%
1/10
|
4.0%
4/99
|
|
Infections and infestations
PNEUMONIA
|
10.0%
1/10
|
3.0%
3/99
|
|
Infections and infestations
ORAL HERPES
|
0.00%
0/10
|
5.1%
5/99
|
|
Infections and infestations
PHARYNGITIS
|
10.0%
1/10
|
3.0%
3/99
|
|
Infections and infestations
FOLLICULITIS
|
0.00%
0/10
|
5.1%
5/99
|
|
Infections and infestations
GASTROENTERITIS
|
10.0%
1/10
|
6.1%
6/99
|
|
Infections and infestations
NASOPHARYNGITIS
|
10.0%
1/10
|
7.1%
7/99
|
|
Infections and infestations
ORAL CANDIDIASIS
|
0.00%
0/10
|
7.1%
7/99
|
|
Infections and infestations
VAGINAL INFECTION
|
10.0%
1/10
|
1.0%
1/99
|
|
Infections and infestations
LOCALISED INFECTION
|
10.0%
1/10
|
1.0%
1/99
|
|
Infections and infestations
CLOSTRIDIAL INFECTION
|
10.0%
1/10
|
1.0%
1/99
|
|
Infections and infestations
FUNGAL SKIN INFECTION
|
10.0%
1/10
|
0.00%
0/99
|
|
Infections and infestations
URINARY TRACT INFECTION
|
10.0%
1/10
|
8.1%
8/99
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
0.00%
0/10
|
7.1%
7/99
|
|
Infections and infestations
URINARY TRACT INFECTION BACTERIAL
|
10.0%
1/10
|
0.00%
0/99
|
|
Infections and infestations
ESCHERICHIA URINARY TRACT INFECTION
|
10.0%
1/10
|
1.0%
1/99
|
|
Metabolism and nutrition disorders
ANOREXIA
|
30.0%
3/10
|
25.3%
25/99
|
|
Metabolism and nutrition disorders
HYPOKALAEMIA
|
0.00%
0/10
|
6.1%
6/99
|
|
Metabolism and nutrition disorders
HYPOCALCAEMIA
|
10.0%
1/10
|
3.0%
3/99
|
|
Metabolism and nutrition disorders
FLUID OVERLOAD
|
10.0%
1/10
|
2.0%
2/99
|
|
Metabolism and nutrition disorders
DECREASED APPETITE
|
10.0%
1/10
|
3.0%
3/99
|
|
Blood and lymphatic system disorders
ANAEMIA
|
10.0%
1/10
|
14.1%
14/99
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
10.0%
1/10
|
3.0%
3/99
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
10.0%
1/10
|
13.1%
13/99
|
|
Blood and lymphatic system disorders
SPLENOMEGALY
|
10.0%
1/10
|
4.0%
4/99
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
0.00%
0/10
|
17.2%
17/99
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
0.00%
0/10
|
6.1%
6/99
|
|
Skin and subcutaneous tissue disorders
ACNE
|
0.00%
0/10
|
6.1%
6/99
|
|
Skin and subcutaneous tissue disorders
RASH
|
20.0%
2/10
|
25.3%
25/99
|
|
Skin and subcutaneous tissue disorders
PURPURA
|
10.0%
1/10
|
4.0%
4/99
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
20.0%
2/10
|
8.1%
8/99
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
0.00%
0/10
|
10.1%
10/99
|
|
Skin and subcutaneous tissue disorders
PETECHIAE
|
10.0%
1/10
|
12.1%
12/99
|
|
Skin and subcutaneous tissue disorders
ECCHYMOSIS
|
0.00%
0/10
|
10.1%
10/99
|
|
Skin and subcutaneous tissue disorders
SKIN ULCER
|
10.0%
1/10
|
0.00%
0/99
|
|
Skin and subcutaneous tissue disorders
SKIN LESION
|
10.0%
1/10
|
4.0%
4/99
|
|
Skin and subcutaneous tissue disorders
NIGHT SWEATS
|
10.0%
1/10
|
9.1%
9/99
|
|
Skin and subcutaneous tissue disorders
HYPERHIDROSIS
|
20.0%
2/10
|
4.0%
4/99
|
|
Skin and subcutaneous tissue disorders
SPIDER NAEVUS
|
10.0%
1/10
|
0.00%
0/99
|
|
Skin and subcutaneous tissue disorders
SWELLING FACE
|
10.0%
1/10
|
0.00%
0/99
|
|
Skin and subcutaneous tissue disorders
PERIORBITAL OEDEMA
|
10.0%
1/10
|
8.1%
8/99
|
|
Reproductive system and breast disorders
NIPPLE PAIN
|
10.0%
1/10
|
0.00%
0/99
|
|
Reproductive system and breast disorders
VAGINAL HAEMORRHAGE
|
10.0%
1/10
|
0.00%
0/99
|
|
Injury, poisoning and procedural complications
CONTUSION
|
10.0%
1/10
|
4.0%
4/99
|
|
Injury, poisoning and procedural complications
SKIN LACERATION
|
10.0%
1/10
|
1.0%
1/99
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
10.0%
1/10
|
11.1%
11/99
|
|
Musculoskeletal and connective tissue disorders
MYOSITIS
|
10.0%
1/10
|
0.00%
0/99
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/10
|
15.2%
15/99
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
10.0%
1/10
|
16.2%
16/99
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
10.0%
1/10
|
15.2%
15/99
|
|
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS
|
10.0%
1/10
|
5.1%
5/99
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/10
|
17.2%
17/99
|
|
Musculoskeletal and connective tissue disorders
MUSCULOSKELETAL PAIN
|
0.00%
0/10
|
6.1%
6/99
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
30.0%
3/10
|
40.4%
40/99
|
|
Respiratory, thoracic and mediastinal disorders
RALES
|
0.00%
0/10
|
5.1%
5/99
|
|
Respiratory, thoracic and mediastinal disorders
HYPOXIA
|
30.0%
3/10
|
2.0%
2/99
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA
|
40.0%
4/10
|
30.3%
30/99
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
0.00%
0/10
|
21.2%
21/99
|
|
Respiratory, thoracic and mediastinal disorders
HAEMOPTYSIS
|
10.0%
1/10
|
6.1%
6/99
|
|
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS
|
0.00%
0/10
|
6.1%
6/99
|
|
Respiratory, thoracic and mediastinal disorders
NASAL DISORDER
|
10.0%
1/10
|
0.00%
0/99
|
|
Respiratory, thoracic and mediastinal disorders
PLEURITIC PAIN
|
10.0%
1/10
|
2.0%
2/99
|
|
Respiratory, thoracic and mediastinal disorders
PLEURAL EFFUSION
|
30.0%
3/10
|
34.3%
34/99
|
|
Respiratory, thoracic and mediastinal disorders
PRODUCTIVE COUGH
|
0.00%
0/10
|
8.1%
8/99
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY OEDEMA
|
10.0%
1/10
|
5.1%
5/99
|
|
Respiratory, thoracic and mediastinal disorders
THROAT TIGHTNESS
|
10.0%
1/10
|
0.00%
0/99
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNOEA EXERTIONAL
|
0.00%
0/10
|
7.1%
7/99
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY FAILURE
|
10.0%
1/10
|
1.0%
1/99
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY THROMBOSIS
|
10.0%
1/10
|
0.00%
0/99
|
|
Respiratory, thoracic and mediastinal disorders
PHARYNGOLARYNGEAL PAIN
|
0.00%
0/10
|
7.1%
7/99
|
|
Respiratory, thoracic and mediastinal disorders
PULMONARY HYPERTENSION
|
10.0%
1/10
|
0.00%
0/99
|
|
Respiratory, thoracic and mediastinal disorders
RESPIRATORY TRACT CONGESTION
|
10.0%
1/10
|
1.0%
1/99
|
|
General disorders
PAIN
|
10.0%
1/10
|
12.1%
12/99
|
|
General disorders
CHILLS
|
0.00%
0/10
|
12.1%
12/99
|
|
General disorders
OEDEMA
|
10.0%
1/10
|
9.1%
9/99
|
|
General disorders
FATIGUE
|
30.0%
3/10
|
34.3%
34/99
|
|
General disorders
PYREXIA
|
80.0%
8/10
|
62.6%
62/99
|
|
General disorders
ASTHENIA
|
50.0%
5/10
|
25.3%
25/99
|
|
General disorders
CHEST PAIN
|
20.0%
2/10
|
13.1%
13/99
|
|
General disorders
FACE OEDEMA
|
10.0%
1/10
|
4.0%
4/99
|
|
General disorders
HYPOTHERMIA
|
10.0%
1/10
|
0.00%
0/99
|
|
General disorders
PITTING OEDEMA
|
10.0%
1/10
|
1.0%
1/99
|
|
General disorders
LOCALISED OEDEMA
|
30.0%
3/10
|
4.0%
4/99
|
|
General disorders
OEDEMA PERIPHERAL
|
30.0%
3/10
|
35.4%
35/99
|
|
General disorders
GENERALISED OEDEMA
|
10.0%
1/10
|
2.0%
2/99
|
|
General disorders
MUCOSAL INFLAMMATION
|
10.0%
1/10
|
5.1%
5/99
|
|
General disorders
INFLUENZA LIKE ILLNESS
|
20.0%
2/10
|
1.0%
1/99
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER