Trial Outcomes & Findings for Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML (NCT NCT00123487)

Last Updated: 2014-11-03

Results Overview

MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm\^3; platelets ≥ 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

638 participants

Primary outcome timeframe

Randomization up to 6 months

Results posted on

2014-11-03

Participant Flow

Study started June 2005; recruitment completed March 2006; study ended June 2013 (Year 7) when the study closed and all participants were off study treatment. Those participants who were resistant or intolerant to prior imatinib were enrolled.

638 participants were enrolled; 27 were not randomized due to: adverse event (1), death (5), other (5), poor/noncompliance (1), no longer met criteria (13), withdrew consent (2). A total of 611 were randomized to treatment; 609 were treated: 2 randomized but not treated due to death (1) and serious adverse event (1).

Participant milestones

Participant milestones
Measure	Dasatinib 140 mg QD Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.
Randomized STARTED	306	305
Randomized COMPLETED	305	304
Randomized NOT COMPLETED	1	1
Treated With Study Drug STARTED	304	305
Treated With Study Drug COMPLETED	0	0
Treated With Study Drug NOT COMPLETED	304	305

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib 140 mg QD Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.
Randomized Death prior to starting treatment	0	1
Randomized SAE prior to starting treatment	1	0
Treated With Study Drug Adverse Event	23	22
Treated With Study Drug Disease Progression	141	122
Treated With Study Drug Physician Decision	8	9
Treated With Study Drug Other	59	58
Treated With Study Drug Study Drug Toxicity	62	80
Treated With Study Drug Withdrawal by Subject	11	13
Treated With Study Drug Unknown (case report form lost)	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Total n=611 Participants Total of all reporting groups
Age, Customized Less than (<) 21 years	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Age, Customized 21 - 45 years	101 participants n=5 Participants	83 participants n=7 Participants	184 participants n=5 Participants
Age, Customized 46 - 65 years	143 participants n=5 Participants	143 participants n=7 Participants	286 participants n=5 Participants
Age, Customized 66 - 75 years	49 participants n=5 Participants	65 participants n=7 Participants	114 participants n=5 Participants
Age, Customized Greater than (>) 75 years	8 participants n=5 Participants	9 participants n=7 Participants	17 participants n=5 Participants
Age, Customized Not Reported	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Sex: Female, Male Female	133 Participants n=5 Participants	134 Participants n=7 Participants	267 Participants n=5 Participants
Sex: Female, Male Male	173 Participants n=5 Participants	171 Participants n=7 Participants	344 Participants n=5 Participants
Race/Ethnicity, Customized Asian	38 participants n=5 Participants	38 participants n=7 Participants	76 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	17 participants n=5 Participants	18 participants n=7 Participants	35 participants n=5 Participants
Race/Ethnicity, Customized White	235 participants n=5 Participants	236 participants n=7 Participants	471 participants n=5 Participants
Race/Ethnicity, Customized Other	13 participants n=5 Participants	9 participants n=7 Participants	22 participants n=5 Participants
Race/Ethnicity, Customized Unknown or Not reported	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 0	138 participants n=5 Participants	134 participants n=7 Participants	272 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 1	121 participants n=5 Participants	109 participants n=7 Participants	230 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 2	40 participants n=5 Participants	58 participants n=7 Participants	98 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ECOG PS 3	7 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Not Reported	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Imatinib Status Primary Resistance	43 participants n=5 Participants	49 participants n=7 Participants	92 participants n=5 Participants
Imatinib Status Acquired Resistance	192 participants n=5 Participants	190 participants n=7 Participants	382 participants n=5 Participants
Imatinib Status Intolerance	67 participants n=5 Participants	65 participants n=7 Participants	132 participants n=5 Participants
Imatinib Status Missing	4 participants n=5 Participants	1 participants n=7 Participants	5 participants n=5 Participants
Participants by Disease Phase Accelerated Phase CML	158 participants n=5 Participants	159 participants n=7 Participants	317 participants n=5 Participants
Participants by Disease Phase Blast Phase CML - Myeloid	75 participants n=5 Participants	74 participants n=7 Participants	149 participants n=5 Participants
Participants by Disease Phase Blast Phase CML - Lymphoid	33 participants n=5 Participants	28 participants n=7 Participants	61 participants n=5 Participants
Participants by Disease Phase Ph+ ALL	40 participants n=5 Participants	44 participants n=7 Participants	84 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization up to 6 months

Population: Participants were analyzed based on the treatment they were randomized to receive (not what they actually received). 95% exact confidence interval (CI) presented.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population	48.0 percentage of participants Interval 42.3 to 53.8	47.9 percentage of participants Interval 42.1 to 53.6

SECONDARY outcome

Timeframe: Randomization up to 2 years

Population: Participants were analyzed based on the treatment they were randomized to receive.

A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population	50.7 percentage of participants Interval 44.9 to 56.4	49.8 percentage of participants Interval 44.1 to 55.6

SECONDARY outcome

Timeframe: Randomization up to 2 years

Population: Participants were analyzed based on the treatment they were randomized to receive. n=number of participants in disease group.

MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm\^3; platelets ≥ 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population Accelerated Phase (n=158, 159)	66.5 percentage of participants Interval 58.5 to 73.8	67.9 percentage of participants Interval 60.1 to 75.1
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population Myeloid Blast Phase (n=75,74)	28.0 percentage of participants Interval 18.2 to 39.6	28.4 percentage of participants Interval 18.5 to 40.1
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population Lymphoid Blast Phase (n=33,28)	42.4 percentage of participants Interval 25.5 to 60.8	32.1 percentage of participants Interval 15.9 to 52.4
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population Ph+ Acute Lymphoblastic Leukemia (n=40,44)	37.5 percentage of participants Interval 22.7 to 54.2	31.8 percentage of participants Interval 18.6 to 47.6

SECONDARY outcome

Timeframe: Day 1 up to 6 months (time of primary endpoint), 2 years

Population: Participants were analyzed based on the treatment they were randomized to receive.

A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Median Time to Major Hematologic Response (MaHR) - Randomized Population 6 Months	1.9 Months Interval 1.8 to 1.9	1.9 Months Interval 1.5 to 2.0
Median Time to Major Hematologic Response (MaHR) - Randomized Population 2 Years	1.9 Months Interval 1.8 to 1.9	1.9 Months Interval 1.6 to 2.1

SECONDARY outcome

Timeframe: Day 1 up to 5 years

Population: Participants who achieved a MaHR during the study.

MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Median duration was measured in months.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=156 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=153 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study	21.1 Months Interval 14.4 to 30.7	24.7 Months Interval 19.5 to 35.6

SECONDARY outcome

Timeframe: Randomization up to 6 Months, 2 Years

Population: Participants were analyzed based on the treatment they were randomized to receive.

Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. MiHR defined as: \< 15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Percent of Participants With Overall Hematologic Response - Randomized Population 6 Months	59.2 percentage of participants Interval 53.4 to 64.7	57.4 percentage of participants Interval 51.6 to 63.0
Percent of Participants With Overall Hematologic Response - Randomized Population 2 Years	60.1 percentage of participants Interval 54.4 to 65.7	59.0 percentage of participants Interval 53.3 to 64.6

SECONDARY outcome

Timeframe: Randomization up to 6 months, 2 years

Population: Participants were analyzed based on the treatment they were randomized to receive.

Type of hematologic response: CHR defined as: WBC ≤ ULN; ANC ≥ 1,000/mm\^3; - platelets ≥ 100,000/mm\^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; \< 5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \<100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. Minor Hematologic Response (MiHR): \<15% blasts in BM and in PB; \< 30% blasts + promyelocytes in BM and PB; \< 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Complete Response, 6 months	94 participants	96 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Complete Response, 2 years	108 participants	110 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population No Evidence of Leukemia, 6 months	53 participants	50 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population No Evidence of Leukemia, 2 years	47 participants	42 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Minor Response, 6 months	34 participants	29 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Minor Response, 2 years	29 participants	28 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population No Response, 6 months	125 participants	130 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population No Response, 2 years	122 participants	125 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population MaHR, 6 months	147 participants	146 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population MaHR, 2 years	155 participants	152 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Overall Response, 6 months	181 participants	175 participants
Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population Overall Response, 2 years	184 participants	180 participants

SECONDARY outcome

Timeframe: Randomization up to 6 Months, 2 Years

Population: Participants were analyzed based on the treatment they were randomized to receive.

Cytogenetic assessments were performed only for the first 2 years of study. 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; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population 6 Months	36.9 percentage of participants Interval 31.5 to 42.6	39.3 percentage of participants Interval 33.8 to 45.1
Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population 2 Years	41.5 percentage of participants Interval 35.9 to 47.2	41.3 percentage of participants Interval 35.7 to 47.1

SECONDARY outcome

Timeframe: Randomization up to 6 Months, 2 Years

Population: Participants were analyzed based on the treatment they were randomized to receive.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Partial CyR, 2 years	30 participants	28 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Unable to determine, 6 months	64 participants	66 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Complete CyR, 6 months	89 participants	84 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Complete CyR, 2 years	97 participants	98 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Partial CyR, 6 months	24 participants	36 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Minor CyR, 6 months	19 participants	18 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Minor CyR, 2 years	13 participants	16 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Minimal CyR, 6 months	47 participants	45 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Minimal CyR, 2 years	43 participants	40 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population No response, 6 months	63 participants	56 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population No response, 2 years	60 participants	51 participants
Number of Participants With Best Cytogenic Response (CyR) - Randomized Population Unable to determine, 2 years	63 participants	72 participants

SECONDARY outcome

Timeframe: Randomization up to 5 Years

Population: Participants were analyzed based on the treatment they were randomized to receive.

PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Median Progression Free Survival (PFS) - Randomized Population	7.8 Months Interval 5.9 to 9.2	10.4 Months Interval 7.4 to 12.1

SECONDARY outcome

Timeframe: Randomization up to 5 Years

Population: Participants were analyzed based on the treatment they were randomized to receive.

OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Median Overall Survival (OS) - Randomized Population	17.7 Months Interval 12.5 to 23.5	22.4 Months Interval 18.0 to 32.1

SECONDARY outcome

Timeframe: 24 months, 36 months, 48 months, 60 months

Population: Participants were analyzed based on the treatment they were randomized to receive. Kaplan-Meir estimates of PFS or OS (95% Confidence Interval) are provided below.

PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=306 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population PFS at 24 Months	29.5 percentage of participants Interval 24.2 to 34.8	33.1 percentage of participants Interval 27.4 to 38.8
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population PFS at 36 Months	24.1 percentage of participants Interval 19.0 to 29.1	26.6 percentage of participants Interval 21.0 to 32.1
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population PFS at 48 Months	19.8 percentage of participants Interval 15.0 to 24.6	20.5 percentage of participants Interval 15.1 to 25.9
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population PFS at 60 Months	16.9 percentage of participants Interval 12.3 to 21.5	15.9 percentage of participants Interval 10.5 to 21.2
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population OS at 24 Months	43.3 percentage of participants Interval 37.5 to 49.0	48.7 percentage of participants Interval 42.9 to 54.5
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population OS at 36 Months	37.1 percentage of participants Interval 31.4 to 42.8	42.5 percentage of participants Interval 36.6 to 48.3
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population OS at 48 Months	32.7 percentage of participants Interval 27.1 to 38.3	38.2 percentage of participants Interval 32.4 to 44.0
Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population OS at 60 Months	28.8 percentage of participants Interval 23.4 to 34.3	36.1 percentage of participants Interval 30.3 to 41.8

SECONDARY outcome

Timeframe: Day 1 to Year 7

Population: All participants who received at least one dose of study drug were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive.

With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=304 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants Deaths	203 participants	186 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants Death within 30 Days	66 participants	63 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants SAEs	228 participants	236 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants AEs Leading to Discontinuation	118 participants	114 participants
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants Drug-related Fluid Retention	109 participants	137 participants

SECONDARY outcome

Timeframe: Baseline to Year 2

Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) version 3.0. CTC Grade 3 and 4 criteria are defined as follows: White blood cells (WBC): Grade (Gr) 3:\<2.0 to 1.0\*10\^9/L, Gr 4:\<1.0\*10\^9/L. Absolute neutrophil count (ANC): Gr 3:\<1.0 to 0.5\*10\^9/L, Gr 4:\<0.5\*10\^9/L. Platelet count Gr 3:\<50.0 to 25.0\*10\^9/L, Gr 4:\<25.0 to 10\^9/L. Hemoglobin Gr 3:\<8.0 to 6.5 g/dL, Gr 4:\<6.5 g/dL. Baseline was laboratory value obtained within 2 weeks prior to randomization.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=304 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants WBC	129 participants	114 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants WBC not reported at baseline	2 participants	2 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants Platelets	64 participants	79 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants Platelets not reported at baseline	2 participants	2 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants Hemoglobin	12 participants	13 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants Hemoglobin not reported at baseline	2 participants	2 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants ANC	127 participants	143 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants ANC not reported at baseline	9 participants	8 participants

SECONDARY outcome

Timeframe: Day 1 up to Year 7

Population: All participants who received at least one dose of study drug and had laboratory evaluations available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive.

Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0. Grade 4 hematology evaluations used to determine myelosuppression included: WBC: \<1.0\*10\^9/L. ANC: \<0.5\*10\^9/L. Platelet count \<25.0 to 10\^9/L.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=299 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=303 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations ANC (n=299, 303)	132 participants	142 participants
Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations WBC (n=299, 303)	64 participants	72 participants
Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations Platelets(n=299, 303)	167 participants	164 participants

SECONDARY outcome

Timeframe: Baseline to Year 2

Laboratory abnormalities were graded according to the NCI CTC version 3.0. Grade 3 and 4 criteria were defined as follows: Upper limit of normal (ULN). Alanine transaminase (ALT) Grade (Gr) 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Aspartate aminotransferase (AST) Gr 3: \>5.0 to 20.0\*ULN; Gr 4: \>20.0\*ULN. Total bilirubin Gr 3: \>3.0 to 10..0\*ULN; Gr 4: \>10.0.0\*ULN. Serum creatinine (H) Gr 3: \>3.0 to 6.0\*ULN; Gr 4: \>6.0\*ULN. Calcium (L) Gr3: 6.0-7.0; Gr 4: \<6.0 mg/dL; Phosphorus (L): Gr 3: \<2.0 - 1.0 mg/dL , Gr 4: \<1.0 mg/dL. Non-hematologic laboratory results were not collected beyond Year 2. Baseline values were obtained within 2 weeks prior to randomization.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=304 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=305 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Hypophosphatemia	28 participants	26 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Phosphorus not reported at baseline	14 participants	20 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Hypocalcemia	14 participants	9 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Calcium not reported at baseline	5 participants	13 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Elevated ALT	8 participants	4 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants ALT not reported at baseline	4 participants	4 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Elevated AST	3 participants	2 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants AST not reported at baseline	3 participants	6 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Elevated Bilirubin	4 participants	3 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Bilirubin not reported at baseline	2 participants	7 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Elevated Serum Creatinine	4 participants	2 participants
Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants Serum Creatinine not reported at baseline	1 participants	3 participants

SECONDARY outcome

Timeframe: Baseline to Year 2

Population: All participants who received at least one dose of study drug and had appropriate baseline and on-study ECG data available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive.

A12-lead electrocardiogram (ECG) was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Days 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. The QT interval corrected with Fridericia formula is presented with categories of changes from baseline (BL) in milliseconds (msec).

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=269 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=257 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants QTcF <-60 msec change from BL	4 participants	7 participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants -60 - < -30 msec change from BL	13 participants	15 participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants -30 - < 0 msec change from BL	88 participants	65 participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants 0 - 30 msec change from BL	114 participants	125 participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants > 30 - 60 msec change from BL	31 participants	24 participants
Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants > 60 msec change from BL	19 participants	21 participants

SECONDARY outcome

Timeframe: Baseline up to Year 2

Population: All participants who received at least one dose of study drug and had appropriate ECG data available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive.

A12-lead ECG was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Day 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. QT Interval corrected with Fridericia formula was measured in msec.

Outcome measures

Outcome measures
Measure	Dasatinib 140 mg QD n=280 Participants Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.	Dasatinib 70 mg BID n=270 Participants Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant..
Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants Maximum QTcF Interval < 450 msec	252 participants	239 participants
Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants Maximum QTcF Interval 450 - 500 msec	21 participants	26 participants
Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants Maximum QTcF Interval > 500 msec	7 participants	5 participants

Adverse Events

Dasatinib 140 mg QD

Serious events: 228 serious events

Other events: 289 other events

Deaths: 0 deaths

Dasatinib 70 mg BID

Serious events: 236 serious events

Other events: 290 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