Trial Outcomes & Findings for Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML (NCT NCT00123474)

Last Updated: 2016-08-25

Results Overview

Cytogenetic response (CyR) was based on the number of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

724 participants

Primary outcome timeframe

6 months

Results posted on

2016-08-25

Participant Flow

Study initiated July 2005 and completed July 2014.

724 participants were enrolled, 670 were randomized, and 662 were treated with study drug. Reasons for non-randomization: 38 no longer met criteria, 8 other reasons, 7 withdrew consent, and 1 death.

Participant milestones

Participant milestones
Measure	Dasatinib 100 mg QD Participants received 100 mg once a day (QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg QD Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 50 mg BID Participants received 50 mg twice a day (BID) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.	Dasatinib 70 mg BID Participants received 70 mg BID until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.
Randomized to Treatment STARTED	167	167	168	168
Randomized to Treatment COMPLETED	166	163	166	167
Randomized to Treatment NOT COMPLETED	1	4	2	1
As Treated at Study Closure STARTED	165	163	167	167
As Treated at Study Closure COMPLETED	0	0	0	0
As Treated at Study Closure NOT COMPLETED	165	163	167	167

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib 100 mg QD Participants received 100 mg once a day (QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg QD Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 50 mg BID Participants received 50 mg twice a day (BID) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.	Dasatinib 70 mg BID Participants received 70 mg BID until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.
Randomized to Treatment Randomized, never treated	1	4	2	1
As Treated at Study Closure not reported when site closed	1	0	1	0
As Treated at Study Closure Adverse Event	10	4	10	8
As Treated at Study Closure Disease Progression	35	42	29	27
As Treated at Study Closure Investigator Request	12	6	7	5
As Treated at Study Closure non-specified	54	47	57	60
As Treated at Study Closure Study Drug Toxicity	39	45	45	51
As Treated at Study Closure Withdrawal by Subject	14	19	18	16

Baseline Characteristics

Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib 100 mg QD n=167 Participants Participants received 100 mg once a day (QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg QD n=167 Participants Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 50 mg BID n=168 Participants Participants received 50 mg twice a day (BID) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.	Dasatinib 70 mg BID n=168 Participants Participants received 70 mg BID until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. After the 2-year analysis, and with Protocol Amendment 02, participants on a BID dosing schedule were allowed to switch to a QD dosing schedule.	Total n=670 Participants Total of all reporting groups
Age, Customized Less than, equal to (<=) 65 years	121 participants n=5 Participants	128 participants n=7 Participants	130 participants n=5 Participants	125 participants n=4 Participants	504 participants n=21 Participants
Age, Customized Greater than (>) 65 years	46 participants n=5 Participants	39 participants n=7 Participants	38 participants n=5 Participants	43 participants n=4 Participants	166 participants n=21 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	97 Participants n=7 Participants	83 Participants n=5 Participants	91 Participants n=4 Participants	354 Participants n=21 Participants
Sex: Female, Male Male	84 Participants n=5 Participants	70 Participants n=7 Participants	85 Participants n=5 Participants	77 Participants n=4 Participants	316 Participants n=21 Participants
Imatinib Status Primary Resistance to Imatinib	75 participants n=5 Participants	78 participants n=7 Participants	88 participants n=5 Participants	81 participants n=4 Participants	322 participants n=21 Participants
Imatinib Status Acquired Resistance to Imatinib	49 participants n=5 Participants	45 participants n=7 Participants	36 participants n=5 Participants	45 participants n=4 Participants	175 participants n=21 Participants
Imatinib Status Intolerant to Imatinib	43 participants n=5 Participants	44 participants n=7 Participants	44 participants n=5 Participants	42 participants n=4 Participants	173 participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months

Population: All randomized imatinib-resistant participants with available data were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=247 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=251 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up	51.8 percentage of Participants Interval 45.4 to 58.2	49.0 percentage of Participants Interval 42.7 to 55.4	—	—

SECONDARY outcome

Timeframe: 24 months

Population: All randomized imatinib-resistant participants with available data were summarized.

CyR was based on the number of Ph+ metaphases among cells in metaphase on a Bone Marrow (BM) sample. The criteria for CyR were as follows: CCyR: 0% Ph+ cells in metaphase in BM; PCyR: \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR. Baseline=closest to, but no later than, the first day of study drug for treated participants and closest to, but no later than, the date of randomization, for those who were randomized but who never received treatment, unless otherwise specified.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=247 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=250 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=248 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=249 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants With MCyR At or Prior to 24 Months Follow-Up	58.3 percentage of Participants Interval 51.9 to 64.5	56.4 percentage of Participants Interval 50.0 to 62.6	57.3 percentage of Participants Interval 50.8 to 63.5	57.4 percentage of Participants Interval 51.0 to 63.7

SECONDARY outcome

Timeframe: 6 months, 24 months

Population: All randomized imatinib-resistant participants with available data were summarized.

A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \< 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); \< 5% myelocytes plus metamyelocytes in PB; Basophils in PB \< 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=124 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=123 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=124 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=127 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up 6 Months (n=124,123,124,127)	86.3 percentage of participants Interval 79.0 to 91.8	85.4 percentage of participants Interval 77.9 to 91.1	91.1 percentage of participants Interval 84.7 to 95.5	87.4 percentage of participants Interval 80.3 to 92.6
Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up 24 Month (n=124,123,124,126)	88.7 percentage of participants Interval 81.8 to 93.7	86.2 percentage of participants Interval 78.8 to 91.7	91.9 percentage of participants Interval 85.7 to 96.1	88.9 percentage of participants Interval 82.1 to 93.8

SECONDARY outcome

Timeframe: 6 months

Population: Randomized imatinib-resistant participants with MCyR and available data were summarized.

Time to MCyR was defined as the time from the first dosing date until criteria were first met for CCyR or PCyR, whichever occurred first. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to MCyR response for responders and time to last cytogenetic assessment for non-responders).

Outcome measures

Outcome measures
Measure	QD Dasatinib n=66 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=62 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=58 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=65 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Time to MCyR in Participants With MCyR at 6 Months Follow-Up	2.8 Months Interval 2.8 to 3.0	2.8 Months Interval 2.8 to 2.9	2.8 Months Interval 2.8 to 2.9	2.8 Months Interval 2.8 to 3.0

SECONDARY outcome

Timeframe: 6 months

Population: Randomized imatinib-resistant participants with CHR and available data were summarized.

Time to CHR was defined as the time from the first dosing date until criteria are first met for the response. Non-responders were censored at the maximum time of all participants in their respective group (ie, maximum between time to CHR response for responders and time to last hematologic assessment for non-responders).

Outcome measures

Outcome measures
Measure	QD Dasatinib n=107 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=105 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=113 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=111 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Time to CHR in Participants With CHR at 6 Months Follow-Up	0.5 Months Interval 0.5 to 0.6	0.5 Months Interval 0.5 to 0.7	0.6 Months Interval 0.6 to 0.9	0.7 Months Interval 0.5 to 0.9

SECONDARY outcome

Timeframe: 24 months

Population: Randomized imatinib-resistant participants with MCyR were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=73 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=71 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=69 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=72 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Time to MCyR in Participants With MCyR at 24 Months Follow-Up	2.9 Months Interval 2.8 to 3.4	2.8 Months Interval 2.8 to 3.0	2.9 Months Interval 2.8 to 3.3	2.9 Months Interval 2.8 to 3.0

SECONDARY outcome

Timeframe: 24 months

Population: Randomized imatinib-resistant participants with CHR were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=110 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=106 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=114 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=112 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Time to CHR in Participants With CHR At 24 Months Follow-Up	0.5 Months Interval 0.5 to 0.6	0.5 Months Interval 0.5 to 0.7	0.6 Months Interval 0.5 to 0.9	0.7 Months Interval 0.5 to 0.9

SECONDARY outcome

Timeframe: 24 months

Population: All imatinib-resistant participants who had achieved MCyR and experienced disease progression were summarized.

Progression in a participant=participant achieved a CHR and no longer met the criteria consistently over consecutive 2-weeks after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to \>20,000/mm\^3 or an increase by \> 50,000/mm\^3 on two assessments performed at least 2 weeks apart; participant met criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a ≥ 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of MCyR, medium duration of MCyR could not be estimated because the majority of participants with MCyR continued to respond, or could not be reliably estimated because of the large number of censored participants. Cytogenetic assessments were not done after the 24 month follow-up.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=73 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=71 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=69 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=72 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Number of Participants With MCyR Whose Disease Progressed by 24 Months	5 participants	17 participants	6 participants	9 participants

SECONDARY outcome

Timeframe: 24 months

Population: All imatinib-resistant participants who achieved CHR and then experienced disease progression were summarized.

Progression in a participant=achieved a CHR and subsequently no longer met the criteria consistently over a consecutive 2-week period after starting their maximum dose; had no CHR after receiving their maximum dose and had an increase in white blood count (WBC) defined as a doubling of the count from the lowest value to \>20,000/mm\^3 or an increase by \> 50,000/mm\^3 on two assessments performed at least 2 weeks apart; met the criteria of accelerated or blast phase CML at any time; had a MCyR and subsequently no longer met the criteria for MCyR after starting their maximum dose; had a ≥ 30% absolute increase in the number of Ph+ metaphases. Although a related secondary endpoint was estimated duration of CHR, medium duration of CHR could not be estimated because the majority of participants with CHR continued to respond, or could not be reliably estimated because of the large number of censored participants.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=110 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=106 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=114 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=112 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Number of Participants With CHR Whose Disease Progressed by 24 Months	18 participants	28 participants	22 participants	24 participants

SECONDARY outcome

Timeframe: Baseline up to 24 months

Population: All randomized, treated participants with available mutation data were summarized.

BCR-ABL mutations were assessed in participants prior to the start of study drug (baseline) and at the time of disease progression or at end of therapy. Quantification of BCR-ABL transcripts in peripheral blood was evaluated using quantitative reverse transcriptase polymerase chain reaction (Q-RT-PCR, RT-PCR).

Outcome measures

Outcome measures
Measure	QD Dasatinib n=147 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=139 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=149 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=146 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants Imatinib-resistant Mutations	49 participants	49 participants	62 participants	48 participants
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants No Mutations	98 participants	87 participants	86 participants	96 participants
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants Mutations with unknown Imatinib-resistance status	0 participants	1 participants	1 participants	2 participants
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants Imatinib Resistant or unknown mutations	49 participants	50 participants	63 participants	50 participants
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants Polymorphisms	0 participants	2 participants	0 participants	0 participants

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All randomized imatinib-resistant participants were summarized.

PFS= time from randomization until: CHR achieved and participant subsequently no longer met criteria for CHR over 2 weeks; no CHR after receiving maximum dose and an increase in WBC (ie, doubling of the count from the lowest value to \> 20,000/mm\^3 or an increase by \> 50,000/mm\^3 on 2 assessments performed 2 weeks apart); participant met criteria of accelerated phase or blast phase CML; participant had MCyR and subsequently no longer met criteria for MCyR after starting maximum dose; participant had a ≥ 30% absolute increase in number of Ph+ metaphases. Deaths without a reported prior progression were considered to have progressed on the date of death; those who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. When first progression reported during follow-up, it was censored at last on-study assessment. If the first progression reported during follow-up was death, participant considered to have progressed at date of death.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=124 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=123 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=124 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=126 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 36 Months (n=124,123,124, 127)	64.8 percentage of participants Interval 55.2 to 72.9	47.4 percentage of participants Interval 37.7 to 56.5	67.1 percentage of participants Interval 57.3 to 75.1	58.2 percentage of participants Interval 48.4 to 66.8
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 24 Months (n=124,123,124, 127)	75.2 percentage of participants Interval 66.3 to 82.1	61.3 percentage of participants Interval 52.7 to 69.6	70.3 percentage of participants Interval 60.8 to 77.9	70.8 percentage of participants Interval 61.6 to 78.2
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 48 Months (n=124,123,124, 127)	57.8 percentage of participants Interval 48.0 to 66.5	40.0 percentage of participants Interval 30.6 to 49.3	63.8 percentage of participants Interval 53.7 to 72.2	55.1 percentage of participants Interval 45.2 to 64.8
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 60 Months (n=124,123,124, 127)	50.2 percentage of participants Interval 40.2 to 59.3	36.4 percentage of participants Interval 27.1 to 45.8	57.4 percentage of participants Interval 46.9 to 66.5	50.2 percentage of participants Interval 40.2 to 59.4
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 72 Months (n=124,123,124, 127)	44.0 percentage of participants Interval 34.0 to 53.6	31.4 percentage of participants Interval 22.4 to 40.8	50.7 percentage of participants Interval 40.0 to 60.4	45.3 percentage of participants Interval 35.2 to 54.8
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 84 Months (n=124,123,124, 127)	39.0 percentage of participants Interval 29.2 to 48.7	30.2 percentage of participants Interval 21.2 to 39.6	42.1 percentage of participants Interval 31.5 to 52.4	41.3 percentage of participants Interval 31.3 to 51.0

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All randomized imatinib-resistant participants were summarized.

Overall survival (OS) was defined as the time from randomization until death. Survival data were collected for up to 5 years on participants who had discontinued dasatinib treatment. Participants who did not die or who were lost to follow-up were censored on the last date the participant was known to be alive.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=124 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=123 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=124 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=126 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 84 Months (n=124,123,124,127)	62.6 percentage of participants Interval 52.6 to 71.0	68.1 percentage of participants Interval 58.0 to 76.2	67.9 percentage of participants Interval 57.9 to 76.0	65.0 percentage of participants Interval 55.3 to 73.0
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 24 Months (n=124,123,124,127)	90.1 percentage of participants Interval 83.2 to 94.2	93.9 percentage of participants Interval 87.6 to 97.0	88.9 percentage of participants Interval 81.6 to 93.4	85.1 percentage of participants Interval 77.3 to 90.3
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 36 Months (n=124,123,124,127)	87.5 percentage of participants Interval 80.2 to 92.3	83.8 percentage of participants Interval 75.6 to 89.5	83.5 percentage of participants Interval 75.3 to 89.1	76.5 percentage of participants Interval 67.7 to 83.1
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 48 Months (n=124,123,124,127)	79.7 percentage of participants Interval 71.3 to 85.9	82.0 percentage of participants Interval 73.4 to 88.0	80.7 percentage of participants Interval 72.1 to 86.9	71.1 percentage of participants Interval 61.9 to 78.4
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 60 Months (n=124,123,124,127)	75.1 percentage of participants Interval 66.1 to 82.0	78.0 percentage of participants Interval 68.9 to 84.7	73.6 percentage of participants Interval 64.1 to 80.9	69.1 percentage of participants Interval 59.8 to 76.7
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up 72 Months (n=124,123,124,127)	67.9 percentage of participants Interval 58.3 to 75.8	72.6 percentage of participants Interval 62.9 to 80.1	71.4 percentage of participants Interval 61.8 to 79.0	67.1 percentage of participants Interval 57.6 to 74.9

SECONDARY outcome

Timeframe: 6 months, 24 months

Population: All randomized imatinib-intolerant participants with available data were summarized.

CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; PCyR: \>0 to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: \>35 to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: \>65 to 95% Ph+ cells in metaphase in BM; No cytogenetic response: \>95 to 100% Ph+ cells in metaphase in BM; Best CyR was defined as the best response obtained at any time during the study; MCyR was defined as a best CyR of CCyR or PCyR.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=87 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=85 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=87 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=86 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose 6 Month	72.4 percentage of participants Interval 61.8 to 81.5	70.6 percentage of participants Interval 59.7 to 80.0	73.6 percentage of participants Interval 63.0 to 82.4	69.4 percentage of participants Interval 58.5 to 79.0
Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose 24 Month	77.0 percentage of participants Interval 66.8 to 85.4	75.6 percentage of participants Interval 65.1 to 84.2	77.0 percentage of participants Interval 66.8 to 85.4	75.6 percentage of participants Interval 65.1 to 84.2

SECONDARY outcome

Timeframe: 6 months, 24 months

Population: All randomized imatinib-intolerant participants were summarized.

A CHR was obtained when all the following criteria were met: White Blood Cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \< 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); \< 5% myelocytes plus metamyelocytes in PB; Basophils in PB \< 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=43 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=44 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=44 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=42 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up 6 Months (n=43,44,44,41)	100 percentage of participants	86 percentage of participants	93 percentage of participants	85 percentage of participants
Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up 24 Months (n=43,44,44,42)	100 percentage of participants	89 percentage of participants	93 percentage of participants	86 percentage of participants

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All randomized imatinib-intolerant participants with available data were summarized

Outcome measures

Outcome measures
Measure	QD Dasatinib n=43 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=44 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=44 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=42 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 72 Months (n=43,44,44,42)	59.2 percentage of participants Interval 40.8 to 73.6	66.5 percentage of participants Interval 46.3 to 80.6	58.2 percentage of participants Interval 39.8 to 72.7	55.2 percentage of participants Interval 35.7 to 71.1
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 84 Months (n=43,44,44,42)	50.9 percentage of participants Interval 32.1 to 67.0	66.5 percentage of participants Interval 46.3 to 80.6	47.5 percentage of participants Interval 27.4 to 65.2	50.2 percentage of participants Interval 30.4 to 67.1
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 24 Months (n=43,44,44,42)	83.6 percentage of participants Interval 67.0 to 92.3	87.7 percentage of participants Interval 72.8 to 94.7	77.4 percentage of participants Interval 61.0 to 87.6	83.7 percentage of participants Interval 67.1 to 92.4
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 36 Months (n=43,44,44,42)	71.7 percentage of participants Interval 53.6 to 83.7	76.0 percentage of participants Interval 58.7 to 86.8	68.6 percentage of participants Interval 51.1 to 80.9	77.4 percentage of participants Interval 59.6 to 88.1
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 48 Months (n=43,44,44,42)	62.7 percentage of participants Interval 44.5 to 76.5	76.0 percentage of participants Interval 58.7 to 86.8	62.0 percentage of participants Interval 44.1 to 75.7	66.9 percentage of participants Interval 47.8 to 80.4
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up 60 Months (n=43,44,44,42)	59.2 percentage of participants Interval 40.8 to 73.6	71.2 percentage of participants Interval 52.1 to 83.8	62.0 percentage of participants Interval 44.1 to 75.7	59.5 percentage of participants Interval 40.1 to 74.4

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All randomized imatinib-intolerant participants were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=43 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=44 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=44 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=42 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 24 Months (n=43,44,44,42)	94.9 percentage of participants Interval 81.2 to 98.7	92.8 percentage of participants Interval 79.2 to 97.6	95.3 percentage of participants Interval 82.5 to 98.8	97.4 percentage of participants Interval 82.8 to 99.6
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 36 Months (n=43,44,44,42)	89.7 percentage of participants Interval 74.9 to 96.0	92.8 percentage of participants Interval 79.2 to 97.6	90.4 percentage of participants Interval 76.4 to 96.3	94.7 percentage of participants Interval 80.6 to 98.7
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 48 Months (n=43,44,44,42)	84.5 percentage of participants Interval 68.6 to 92.7	87.5 percentage of participants Interval 72.4 to 94.6	85.1 percentage of participants Interval 69.7 to 93.0	86.8 percentage of participants Interval 71.2 to 94.3
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 60 Months (n=43,44,44,42)	81.8 percentage of participants Interval 65.6 to 90.9	87.5 percentage of participants Interval 72.4 to 94.6	82.4 percentage of participants Interval 66.6 to 91.2	81.1 percentage of participants Interval 64.3 to 90.5
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 72 Months (n=43,44,44,42)	79.0 percentage of participants Interval 62.3 to 88.9	87.5 percentage of participants Interval 72.4 to 94.6	79.6 percentage of participants Interval 63.2 to 89.3	81.1 percentage of participants Interval 64.3 to 90.5
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up 84 Months (n=43,44,44,42)	70.0 percentage of participants Interval 52.2 to 82.2	87.5 percentage of participants Interval 72.4 to 94.6	76.6 percentage of participants Interval 59.7 to 87.2	77.7 percentage of participants Interval 60.1 to 88.2

SECONDARY outcome

Timeframe: 6 months

Population: All randomized participants were summarized.

Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM. Partial cytogenetic response (PCyR): \>0 to 35% Ph+ cells in metaphase in BM. MCyR: best cytogenetic response of CCyR or PCyR. A complete hematologic response (CHR) was obtained when all the following criteria were met: White Blood Cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \< 450,000/mm³; No blasts or promyelocytes in peripheral blood (PB); \< 5% myelocytes plus metamyelocytes in PB; Basophils in PB \< 20%; No extramedullary involvement (including no splenomegaly or hepatomegaly). Hematologic responses were counted anytime following 14 days after the dosing start date.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=334 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=336 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=335 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=335 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 6 Months Follow-Up MCyR (n=334,336,335,335)	57.2 percentage of participants Interval 51.7 to 62.6	54.5 percentage of participants Interval 49.0 to 59.9	56.1 percentage of participants Interval 50.6 to 61.5	55.5 percentage of participants Interval 50.0 to 60.9
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 6 Months Follow-Up CHR(n=334,336,335,335)	87.7 percentage of participants Interval 83.7 to 91.0	89.3 percentage of participants Interval 85.5 to 92.4	90.7 percentage of participants Interval 87.1 to 93.6	86.3 percentage of participants Interval 82.1 to 89.8

SECONDARY outcome

Timeframe: 24 months

Population: All randomized participants were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=334 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=336 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=335 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=335 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 24 Months Follow-Up MCyR(n=334,336,335,335)	63.2 percentage of participants Interval 57.8 to 68.4	61.3 percentage of participants Interval 55.9 to 66.5	62.4 percentage of participants Interval 57.0 to 67.6	62.1 percentage of participants Interval 56.7 to 67.3
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 24 Months Follow-Up CHR (n=334,336,335,335)	89.2 percentage of participants Interval 85.4 to 92.3	90.2 percentage of participants Interval 86.5 to 93.1	91.9 percentage of participants Interval 88.5 to 94.6	87.5 percentage of participants Interval 83.4 to 90.8

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All participants who were randomized to a treatment arm were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=167 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=167 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=168 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=168 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 24 Months (n=167, 167, 168, 168)	77.4 percentage of participants Interval 69.9 to 83.2	67.7 percentage of participants Interval 59.6 to 74.5	72.2 percentage of participants Interval 64.3 to 78.7	73.9 percentage of participants Interval 66.1 to 80.1
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 36 Months (n=167, 167, 168, 168)	66.6 percentage of participants Interval 58.3 to 73.6	54.0 percentage of participants Interval 45.4 to 61.8	67.5 percentage of participants Interval 59.2 to 74.5	62.8 percentage of participants Interval 54.3 to 70.1
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 48 Months (n=167, 167, 168, 168)	59.1 percentage of participants Interval 50.6 to 66.6	48.0 percentage of participants Interval 39.4 to 56.2	63.3 percentage of participants Interval 54.8 to 70.7	58.7 percentage of participants Interval 50.1 to 66.3
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 60 Months (n=167, 167, 168, 168)	52.5 percentage of participants Interval 43.8 to 60.5	44.2 percentage of participants Interval 35.5 to 52.5	58.7 percentage of participants Interval 49.8 to 66.5	52.5 percentage of participants Interval 43.7 to 60.5
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 72 Months (n=167, 167, 168, 168)	40.0 percentage of participants Interval 39.2 to 56.2	39.2 percentage of participants Interval 30.6 to 47.7	52.8 percentage of participants Interval 43.7 to 61.1	47.7 percentage of participants Interval 38.7 to 56.0
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants 84 Months (n=167, 167, 168, 168)	42.1 percentage of participants Interval 33.4 to 50.6	38.2 percentage of participants Interval 29.6 to 46.7	43.9 percentage of participants Interval 34.5 to 52.9	43.5 percentage of participants Interval 34.5 to 52.1

SECONDARY outcome

Timeframe: 24, 36, 48, 60, 72, and 84 months

Population: All participants who were randomized to a treatment arm were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=167 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=167 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=168 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=168 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 24 Months (n=167, 167, 168, 168)	91.3 percentage of participants Interval 85.8 to 94.8	93.6 percentage of participants Interval 88.4 to 96.5	90.6 percentage of participants Interval 84.9 to 94.2	88.1 percentage of participants Interval 81.9 to 92.2
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 72 Months (n=167, 167, 168, 168)	70.9 percentage of participants Interval 62.9 to 77.5	76.6 percentage of participants Interval 68.7 to 82.7	73.6 percentage of participants Interval 65.6 to 80.0	70.5 percentage of participants Interval 62.5 to 77.1
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 36 Months (n=167, 167, 168, 168)	88.1 percentage of participants Interval 82.0 to 92.3	86.2 percentage of participants Interval 79.6 to 90.8	85.3 percentage of participants Interval 78.7 to 90.0	80.9 percentage of participants Interval 73.9 to 86.3
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 48 Months (n=167, 167, 168, 168)	81.0 percentage of participants Interval 73.9 to 86.3	83.4 percentage of participants Interval 76.4 to 88.5	81.8 percentage of participants Interval 74.7 to 87.1	74.9 percentage of participants Interval 67.3 to 81.0
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 60 Months (n=167, 167, 168, 168)	76.8 percentage of participants Interval 69.4 to 82.7	80.5 percentage of participants Interval 73.1 to 86.0	75.9 percentage of participants Interval 68.2 to 82.0	72.0 percentage of participants Interval 64.1 to 78.4
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants 84 Months (n=167, 167, 168, 168)	64.6 percentage of participants Interval 56.1 to 71.8	73.4 percentage of participants Interval 65.2 to 79.9	70.3 percentage of participants Interval 62.0 to 77.1	68.1 percentage of participants Interval 59.8 to 74.9

SECONDARY outcome

Timeframe: Baseline to 30 days post last dose, up to 24 months

Population: All randomized participants who received at least one dose of study drug were summarized.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=165 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=163 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=167 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose n=167 Participants Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up Drug-Related SAE	32 participants	40 participants	47 participants	55 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up Drug-Related AEs that led to discontinuationt	14 participants	24 participants	20 participants	25 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up Any SAE	58 participants	67 participants	73 participants	78 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up Death within 30 days of last dose	3 participants	2 participants	6 participants	5 participants

SECONDARY outcome

Timeframe: Baseline to 30 days post last dose, up to 7 years (study closure July 2014)

Population: All randomized participants who received at least one dose of study drug were summarized.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Baseline=closest to, but no later than, the first day of study drug for treated participants. After the 2-year analysis and Protocol Amendment 02, those on a BID dosing schedule were allowed to switch to a QD dosing schedule. Due to the large number of participants switching from BID dosing to QD dosing, the abbreviated dosing data collection method incorporated in Amendment 03, the overall safety data are presented for the 100 mg QD group and combined for the other treatment groups.

Outcome measures

Outcome measures
Measure	QD Dasatinib n=165 Participants Participants received either 100 mg or 140 mg once a day (QD) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	BID Dasatinib n=497 Participants Participants received either 50 mg or 70 mg twice a day (BID) dasatinib until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 100 mg Total Daily Dose n=662 Participants Participants received 100 mg as a total daily dose (either 50 mg BID or 100 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.	Dasatinib 140 mg Total Daily Dose Participants received 140 mg as a total daily dose (either 70 mg BID or 140 mg QD) until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw.
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up AEs Leading to Discontinuation of Treatment	43 participants	153 participants	196 participants	—
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up All Deaths	51 participants	133 participants	184 participants	—
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up Deaths on-study or within 30 days post dose	11 participants	15 participants	26 participants	—
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up SAEs	75 participants	259 participants	334 participants	—

Adverse Events

100mg QD

Serious events: 75 serious events

Other events: 160 other events

Deaths: 0 deaths

140mg QD

Serious events: 78 serious events

Other events: 155 other events

Deaths: 0 deaths

50mg BID

Serious events: 89 serious events

Other events: 160 other events

Deaths: 0 deaths

70mg BID

Serious events: 92 serious events

Other events: 165 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

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