Myeloid Leukemia, Chronic, Chronic-Phase
Conditions
Keywords
Chronic Phase Chronic Myelogenous Leukemia
Brief summary
This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia chromosome or BCR-ABL positive chronic myelogenous leukemia, who are resistant or intolerant to imatinib mesylate (Gleevec).
Interventions
DRUGdasatinib
Tablets, Oral, 50 mg BID, indefinitely, survival study
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com. Inclusion Criteria: * Subjects with Philadelphia chromosome positive (Ph+) (or BCR/ABL+) chronic phase chronic myeloid leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate. * Men and women, 18 years or older * Adequate hepatic function * Adequate renal function * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized.
Exclusion criteria
* Women who are pregnant or breastfeeding * Subjects who are eligible and willing to undergo transplantation during the screening period * A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy * Uncontrolled or significant cardiovascular disease * Medications that increase bleeding risk * Medications that change heart rhythms * Dementia or altered mental status that would prohibit the understanding or rendering of informed consent * History of significant bleeding disorder unrelated to CML * Concurrent incurable malignancy other than CML * Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy * Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up | 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 6 months, 24 months | 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. |
| Time to MCyR in Participants With MCyR at 6 Months Follow-Up | 6 months | 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). |
| Time to CHR in Participants With CHR at 6 Months Follow-Up | 6 months | 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). |
| Time to MCyR in Participants With MCyR at 24 Months Follow-Up | 24 months | 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). Cytogenetic assessments were not done after the 2 Year Follow-up. |
| Time to CHR in Participants With CHR At 24 Months Follow-Up | 24 months | 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). Cytogenetic assessments were not done after the 2 Year Follow-up. |
| Number of Participants With MCyR Whose Disease Progressed by 24 Months | 24 months | 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. |
| Number of Participants With CHR Whose Disease Progressed by 24 Months | 24 months | 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. |
| Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Baseline up to 24 months | 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). |
| Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up | 24, 36, 48, 60, 72, and 84 months | 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. |
| Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up | 24, 36, 48, 60, 72, and 84 months | 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. |
| Percent of Participants With MCyR At or Prior to 24 Months Follow-Up | 24 months | 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. |
| Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 6 months, 24 months | 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. |
| Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up | 24, 36, 48, 60, 72, and 84 months | 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. |
| Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up | 24, 36, 48, 60, 72, and 84 months | 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. |
| 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 | 6 months | 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. |
| 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 | 24 months | 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. No cytogenic assessments were made after 2 years of follow-up. |
| 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, 36, 48, 60, 72, and 84 months | 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. |
| Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants | 24, 36, 48, 60, 72, and 84 months | 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. |
| Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up | Baseline to 30 days post last dose, up to 24 months | 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. |
| Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | Baseline to 30 days post last dose, up to 7 years (study closure July 2014) | 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. |
| 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 months, 24 months | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Mexico, Netherlands, Norway, Peru, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
Study initiated July 2005 and completed July 2014.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 167 |
| Dasatinib 140 mg QD Participants received 140 mg QD until progression of disease, development of intolerable toxicity, or the participant's decision to withdraw. | 167 |
| 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. | 168 |
| 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. | 168 |
| Total | 670 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| 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 | not reported when site closed | 1 | 0 | 1 | 0 |
| As Treated at Study Closure | Study Drug Toxicity | 39 | 45 | 45 | 51 |
| As Treated at Study Closure | Withdrawal by Subject | 14 | 19 | 18 | 16 |
| Randomized to Treatment | Randomized, never treated | 1 | 4 | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Dasatinib 100 mg QD | Dasatinib 140 mg QD | Dasatinib 50 mg BID | Dasatinib 70 mg BID |
|---|---|---|---|---|---|
| Age, Customized Greater than (>) 65 years | 166 participants | 46 participants | 39 participants | 38 participants | 43 participants |
| Age, Customized Less than, equal to (<=) 65 years | 504 participants | 121 participants | 128 participants | 130 participants | 125 participants |
| Imatinib Status Acquired Resistance to Imatinib | 175 participants | 49 participants | 45 participants | 36 participants | 45 participants |
| Imatinib Status Intolerant to Imatinib | 173 participants | 43 participants | 44 participants | 44 participants | 42 participants |
| Imatinib Status Primary Resistance to Imatinib | 322 participants | 75 participants | 78 participants | 88 participants | 81 participants |
| Sex: Female, Male Female | 354 Participants | 83 Participants | 97 Participants | 83 Participants | 91 Participants |
| Sex: Female, Male Male | 316 Participants | 84 Participants | 70 Participants | 85 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 160 / 165 | 155 / 163 | 160 / 167 | 165 / 167 |
| serious Total, serious adverse events | 75 / 165 | 78 / 163 | 89 / 167 | 92 / 167 |
Outcome results
Primary
Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up
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.
Time frame: 6 months
Population: All randomized imatinib-resistant participants with available data were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QD Dasatinib | Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up | 51.8 percentage of Participants |
| BID Dasatinib | Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up | 49.0 percentage of Participants |
Comparison: 6 Month Analysis95% CI: [-6, 11.6]
Secondary
Number of Participants With CHR Whose Disease Progressed by 24 Months
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.
Time frame: 24 months
Population: All imatinib-resistant participants who achieved CHR and then experienced disease progression were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QD Dasatinib | Number of Participants With CHR Whose Disease Progressed by 24 Months | 18 participants |
| BID Dasatinib | Number of Participants With CHR Whose Disease Progressed by 24 Months | 28 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With CHR Whose Disease Progressed by 24 Months | 22 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With CHR Whose Disease Progressed by 24 Months | 24 participants |
Secondary
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | SAEs | 75 participants |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | SAEs | 259 participants |
| BID Dasatinib | 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 | 15 participants |
| BID Dasatinib | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | All Deaths | 133 participants |
| BID Dasatinib | 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 | 153 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 26 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | All Deaths | 184 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 196 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up | SAEs | 334 participants |
Secondary
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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 | 40 participants |
| BID Dasatinib | 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 | 24 participants |
| BID Dasatinib | 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 | 2 participants |
| BID Dasatinib | 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 | 67 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 20 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 47 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 6 participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 73 participants |
| Dasatinib 140 mg Total Daily Dose | 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 | 5 participants |
| Dasatinib 140 mg Total Daily Dose | 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 | 55 participants |
| Dasatinib 140 mg Total Daily Dose | 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 | 78 participants |
| Dasatinib 140 mg Total Daily Dose | 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 | 25 participants |
Secondary
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants
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).
Time frame: Baseline up to 24 months
Population: All randomized, treated participants with available mutation data were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Polymorphisms | 0 participants |
| QD Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Mutations with unknown Imatinib-resistance status | 0 participants |
| QD Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | No Mutations | 98 participants |
| QD Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib Resistant or unknown mutations | 49 participants |
| QD Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib-resistant Mutations | 49 participants |
| BID Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib Resistant or unknown mutations | 50 participants |
| BID Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Polymorphisms | 2 participants |
| BID Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | No Mutations | 87 participants |
| BID Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Mutations with unknown Imatinib-resistance status | 1 participants |
| BID Dasatinib | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib-resistant Mutations | 49 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib Resistant or unknown mutations | 63 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib-resistant Mutations | 62 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Mutations with unknown Imatinib-resistance status | 1 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Polymorphisms | 0 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | No Mutations | 86 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Polymorphisms | 0 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Mutations with unknown Imatinib-resistance status | 2 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib-resistant Mutations | 48 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | Imatinib Resistant or unknown mutations | 50 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants | No Mutations | 96 participants |
Secondary
Number of Participants With MCyR Whose Disease Progressed by 24 Months
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.
Time frame: 24 months
Population: All imatinib-resistant participants who had achieved MCyR and experienced disease progression were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QD Dasatinib | Number of Participants With MCyR Whose Disease Progressed by 24 Months | 5 participants |
| BID Dasatinib | Number of Participants With MCyR Whose Disease Progressed by 24 Months | 17 participants |
| Dasatinib 100 mg Total Daily Dose | Number of Participants With MCyR Whose Disease Progressed by 24 Months | 6 participants |
| Dasatinib 140 mg Total Daily Dose | Number of Participants With MCyR Whose Disease Progressed by 24 Months | 9 participants |
Secondary
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
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. No cytogenic assessments were made after 2 years of follow-up.
Time frame: 24 months
Population: All randomized participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 90.2 percentage of participants |
| BID Dasatinib | 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) | 61.3 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 62.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 91.9 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 62.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 87.5 percentage of participants |
Secondary
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
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.
Time frame: 6 months
Population: All randomized participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 54.5 percentage of participants |
| BID Dasatinib | 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) | 89.3 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 56.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 90.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 86.3 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 55.5 percentage of participants |
Secondary
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All randomized imatinib-intolerant participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 87.5 percentage of participants |
| BID Dasatinib | 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) | 87.5 percentage of participants |
| BID Dasatinib | 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) | 92.8 percentage of participants |
| BID Dasatinib | 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) | 87.5 percentage of participants |
| BID Dasatinib | 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) | 87.5 percentage of participants |
| BID Dasatinib | 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) | 92.8 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 90.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 79.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 85.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 76.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 82.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 95.3 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 81.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 94.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 81.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 86.8 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 97.4 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 77.7 percentage of participants |
Secondary
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All randomized imatinib-intolerant participants with available data were summarized
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 76.0 percentage of participants |
| BID Dasatinib | 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) | 76.0 percentage of participants |
| BID Dasatinib | 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) | 87.7 percentage of participants |
| BID Dasatinib | 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) | 66.5 percentage of participants |
| BID Dasatinib | 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) | 71.2 percentage of participants |
| BID Dasatinib | 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) | 66.5 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 77.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 68.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 47.5 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 62.0 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 58.2 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 62.0 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 50.2 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 83.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 77.4 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 66.9 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 59.5 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 55.2 percentage of participants |
Secondary
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All randomized imatinib-resistant participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 82.0 percentage of participants |
| BID Dasatinib | 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) | 93.9 percentage of participants |
| BID Dasatinib | 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) | 83.8 percentage of participants |
| BID Dasatinib | 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) | 78.0 percentage of participants |
| BID Dasatinib | 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) | 72.6 percentage of participants |
| BID Dasatinib | 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) | 68.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 83.5 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 73.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 67.9 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 71.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 88.9 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 80.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 76.5 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 65.0 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 67.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 69.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 85.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 71.1 percentage of participants |
Secondary
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All randomized imatinib-resistant participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 40.0 percentage of participants |
| BID Dasatinib | 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) | 61.3 percentage of participants |
| BID Dasatinib | 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) | 47.4 percentage of participants |
| BID Dasatinib | 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) | 36.4 percentage of participants |
| BID Dasatinib | 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) | 31.4 percentage of participants |
| BID Dasatinib | 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) | 30.2 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 42.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 63.8 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 50.7 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 67.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 57.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 70.3 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 70.8 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 55.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 45.3 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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 |
| Dasatinib 140 mg Total Daily Dose | 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) | 41.3 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 58.2 percentage of participants |
Secondary
Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up
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.
Time frame: 6 months, 24 months
Population: All randomized imatinib-intolerant participants were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 24 Months (n=43,44,44,42) | 89 percentage of participants |
| BID Dasatinib | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 6 Months (n=43,44,44,41) | 86 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 24 Months (n=43,44,44,42) | 93 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 6 Months (n=43,44,44,41) | 93 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 24 Months (n=43,44,44,42) | 86 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up | 6 Months (n=43,44,44,41) | 85 percentage of participants |
Secondary
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
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.
Time frame: 6 months, 24 months
Population: All randomized imatinib-intolerant participants with available data were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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 | 75.6 percentage of participants |
| BID Dasatinib | 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 | 70.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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 | 73.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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 |
| Dasatinib 140 mg Total Daily Dose | 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 | 69.4 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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 | 75.6 percentage of participants |
Comparison: 6 Month Analysis95% CI: [-11.7, 15.3]
Comparison: 6 Month Analysis95% CI: [-9.3, 17.6]
Comparison: 24 Month Analysis95% CI: [-11.2, 14.1]
Comparison: 24 Month Analysis95% CI: [-11.2, 14.1]
Secondary
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All participants who were randomized to a treatment arm were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 73.4 percentage of participants |
| BID Dasatinib | 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) | 80.5 percentage of participants |
| BID Dasatinib | 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) | 93.6 percentage of participants |
| BID Dasatinib | 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) | 83.4 percentage of participants |
| BID Dasatinib | 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) | 86.2 percentage of participants |
| BID Dasatinib | 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) | 76.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 85.3 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 81.8 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 75.9 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 70.3 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 73.6 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 90.6 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 70.5 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 68.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 80.9 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 72.0 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 88.1 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 74.9 percentage of participants |
Secondary
Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up
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.
Time frame: 6 months, 24 months
Population: All randomized imatinib-resistant participants with available data were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 24 Month (n=124,123,124,126) | 86.2 percentage of participants |
| BID Dasatinib | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 6 Months (n=124,123,124,127) | 85.4 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 6 Months (n=124,123,124,127) | 91.1 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 24 Month (n=124,123,124,126) | 91.9 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 6 Months (n=124,123,124,127) | 87.4 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up | 24 Month (n=124,123,124,126) | 88.9 percentage of participants |
Secondary
Percent of Participants With MCyR At or Prior to 24 Months Follow-Up
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.
Time frame: 24 months
Population: All randomized imatinib-resistant participants with available data were summarized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| QD Dasatinib | Percent of Participants With MCyR At or Prior to 24 Months Follow-Up | 58.3 percentage of Participants |
| BID Dasatinib | Percent of Participants With MCyR At or Prior to 24 Months Follow-Up | 56.4 percentage of Participants |
| Dasatinib 100 mg Total Daily Dose | Percent of Participants With MCyR At or Prior to 24 Months Follow-Up | 57.3 percentage of Participants |
| Dasatinib 140 mg Total Daily Dose | Percent of Participants With MCyR At or Prior to 24 Months Follow-Up | 57.4 percentage of Participants |
95% CI: [-6.8, 10.6]
95% CI: [-8.9, 8.5]
Secondary
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
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.
Time frame: 24, 36, 48, 60, 72, and 84 months
Population: All participants who were randomized to a treatment arm were summarized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| QD Dasatinib | 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 |
| BID Dasatinib | 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) | 48.0 percentage of participants |
| BID Dasatinib | 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) | 54.0 percentage of participants |
| BID Dasatinib | 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) | 67.7 percentage of participants |
| BID Dasatinib | 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) | 44.2 percentage of participants |
| BID Dasatinib | 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) | 39.2 percentage of participants |
| BID Dasatinib | 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) | 38.2 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 63.3 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 43.9 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 72.2 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 67.5 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 58.7 percentage of participants |
| Dasatinib 100 mg Total Daily Dose | 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) | 52.8 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 58.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 62.8 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 43.5 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 47.7 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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) | 73.9 percentage of participants |
| Dasatinib 140 mg Total Daily Dose | 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 |
Secondary
Time to CHR in Participants With CHR At 24 Months Follow-Up
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). Cytogenetic assessments were not done after the 2 Year Follow-up.
Time frame: 24 months
Population: Randomized imatinib-resistant participants with CHR were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QD Dasatinib | Time to CHR in Participants With CHR At 24 Months Follow-Up | 0.5 Months |
| BID Dasatinib | Time to CHR in Participants With CHR At 24 Months Follow-Up | 0.5 Months |
| Dasatinib 100 mg Total Daily Dose | Time to CHR in Participants With CHR At 24 Months Follow-Up | 0.6 Months |
| Dasatinib 140 mg Total Daily Dose | Time to CHR in Participants With CHR At 24 Months Follow-Up | 0.7 Months |
Secondary
Time to CHR in Participants With CHR at 6 Months Follow-Up
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).
Time frame: 6 months
Population: Randomized imatinib-resistant participants with CHR and available data were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QD Dasatinib | Time to CHR in Participants With CHR at 6 Months Follow-Up | 0.5 Months |
| BID Dasatinib | Time to CHR in Participants With CHR at 6 Months Follow-Up | 0.5 Months |
| Dasatinib 100 mg Total Daily Dose | Time to CHR in Participants With CHR at 6 Months Follow-Up | 0.6 Months |
| Dasatinib 140 mg Total Daily Dose | Time to CHR in Participants With CHR at 6 Months Follow-Up | 0.7 Months |
Secondary
Time to MCyR in Participants With MCyR at 24 Months Follow-Up
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). Cytogenetic assessments were not done after the 2 Year Follow-up.
Time frame: 24 months
Population: Randomized imatinib-resistant participants with MCyR were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QD Dasatinib | Time to MCyR in Participants With MCyR at 24 Months Follow-Up | 2.9 Months |
| BID Dasatinib | Time to MCyR in Participants With MCyR at 24 Months Follow-Up | 2.8 Months |
| Dasatinib 100 mg Total Daily Dose | Time to MCyR in Participants With MCyR at 24 Months Follow-Up | 2.9 Months |
| Dasatinib 140 mg Total Daily Dose | Time to MCyR in Participants With MCyR at 24 Months Follow-Up | 2.9 Months |
Secondary
Time to MCyR in Participants With MCyR at 6 Months Follow-Up
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).
Time frame: 6 months
Population: Randomized imatinib-resistant participants with MCyR and available data were summarized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| QD Dasatinib | Time to MCyR in Participants With MCyR at 6 Months Follow-Up | 2.8 Months |
| BID Dasatinib | Time to MCyR in Participants With MCyR at 6 Months Follow-Up | 2.8 Months |
| Dasatinib 100 mg Total Daily Dose | Time to MCyR in Participants With MCyR at 6 Months Follow-Up | 2.8 Months |
| Dasatinib 140 mg Total Daily Dose | Time to MCyR in Participants With MCyR at 6 Months Follow-Up | 2.8 Months |