Chronic Myeloid Leukemia, Philadelphia-Positive Myeloid Leukemia
Conditions
Keywords
Chronic phase Philadelphia chromosome chronic myeloid leukemia (Ph+CML)
Brief summary
The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.
Interventions
DRUGDasatinib
Tablets; oral; 70 mg BID, depending on response
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age of 18 years and older. * Chronic myeloid leukemia (CML) * Previous treatment with imatinib at a dose of \>600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR * CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR * Intolerance to imatinib at any dose * Adequate organ function * Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.
Exclusion criteria
* Woman who are pregnant or breastfeeding * Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above * Previous diagnosis of accelerated phase or blast crisis CML. * Participants who are eligible and willing to undergo transplantation during the screening period * Uncontrolled or significant cardiovascular disease * Use of imatinib within 7 days. * Use of interferon or cytarabine within 14 days * Use of a targeted small-molecule anticancer agent within 14 days * Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants * Prior therapy with dasatinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR) | 2 years | Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Imatinib-intolerant Participants With MCyR | Baseline to 2 years | Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases. |
| Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months | 12 and 24 Months | Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases. |
| Median Time From First Dosing Date to Date of MCyR | Baseline (within 4 weeks of Day 1) and every 12 weeks | MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases. |
| Number of Participants With Complete Hematologic Response (CHR) | Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study | CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months | 12 and 24 months | Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Median Time From First Dosing Until CHR | Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study | CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Number of Participants With Major Molecular Response (MMR) | Baseline to 2 years | MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor. |
| Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria. | Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics. |
| Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Continuously, from baseline through 2 years | AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death) |
| Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Continuously, from baseline through 2 years | AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death) |
| Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib | Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose. | Blood samples were collected for PK to be included in separate population PK analyses. |
Countries
Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Netherlands, Norway, Peru, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imatinib-intolerant Imatinib intolerance was defined as: Grade 3 or greater nonhematologic toxicity that is imatinib-related or Grade 4 hematologic toxicity that is imatinib-related lasting more than 7 days. | 99 |
| Imatinib-resistant Imatinib resistance, acquired or primary. Acquired resistance: participants who achieve major cytogenetic response (MCyR) or complete hematologic response (CHR) on imatinib at any dose prior to progression, defined by 1 of the following: loss of MCyR, loss of CHR, or increasing white blood cell (WBC) count. Primary resistance: participants who never achieve MCyR or CHR at any dose, and meet 1 of the following: continuously increasing WBC count on at least 2 consecutive evaluations at least 2 weeks apart, with the final assessment showing a doubling of WBC from nadir to ≥20,000/mm\^3; an absolute increase in WBC by more than 50,000/mm\^3 above lowest count after starting imatinib; no CHR after 3 months; no cytogenetic response (CyR) after 6 months; or no MCyR after 12 months. Resistance was also defined as chronic myeloid leukemia (CML) with resistance to imatinib ≤600mg/d with genetic mutation in BCR-ABL gene (L248V, G250E, Q252H/R, Y253H/F, E255K/V, T315I/D, F317L, H369P/R). | 288 |
| Total | 387 |
Baseline characteristics
| Characteristic | Total | Imatinib-intolerant | Imatinib-resistant |
|---|---|---|---|
| Age Continuous | 55.4 Years STANDARD_DEVIATION 13.3 | 54.6 Years STANDARD_DEVIATION 12.5 | 55.7 Years STANDARD_DEVIATION 13.5 |
| Age, Customized > 75 years | 16 Participants | 2 Participants | 14 Participants |
| Age, Customized Between 21 and 45 years | 103 Participants | 25 Participants | 78 Participants |
| Age, Customized Between 46 and 65 years | 186 Participants | 55 Participants | 131 Participants |
| Age, Customized Between 66 and 75 years | 82 Participants | 17 Participants | 65 Participants |
| Functional Assessment of Cancer Therapy-General (FACT-G) EWB | 18.1 Units on a scale STANDARD_DEVIATION 3.8 | 17.3 Units on a scale STANDARD_DEVIATION 4 | 18.4 Units on a scale STANDARD_DEVIATION 3.7 |
| Functional Assessment of Cancer Therapy-General (FACT-G) FWB | 19.4 Units on a scale STANDARD_DEVIATION 5.6 | 18.7 Units on a scale STANDARD_DEVIATION 5.5 | 19.6 Units on a scale STANDARD_DEVIATION 5.6 |
| Functional Assessment of Cancer Therapy-General (FACT-G) PWB | 21.7 Units on a scale STANDARD_DEVIATION 5.2 | 22.0 Units on a scale STANDARD_DEVIATION 5.1 | 21.6 Units on a scale STANDARD_DEVIATION 5.2 |
| Functional Assessment of Cancer Therapy-General (FACT-G) SWB | 23.0 Units on a scale STANDARD_DEVIATION 4.4 | 23.0 Units on a scale STANDARD_DEVIATION 4.4 | 23.0 Units on a scale STANDARD_DEVIATION 4.5 |
| Functional Assessment of Cancer Therapy-General (FACT-G) Total FACT-G | 82.1 Units on a scale STANDARD_DEVIATION 13.4 | 81.1 Units on a scale STANDARD_DEVIATION 14.4 | 82.4 Units on a scale STANDARD_DEVIATION 13.1 |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 0 | 276 Participants | 71 Participants | 205 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 1 | 105 Participants | 28 Participants | 77 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 2 | 3 Participants | 0 Participants | 3 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 3 | 0 Participants | 0 Participants | 0 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 4 | 0 Participants | 0 Participants | 0 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score 5 | 0 Participants | 0 Participants | 0 Participants |
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score Not reported | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 13 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Black/African American | 15 Participants | 2 Participants | 13 Participants |
| Race/Ethnicity, Customized Not reported | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 13 Participants | 1 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 345 Participants | 93 Participants | 252 Participants |
| Sex: Female, Male Female | 196 Participants | 57 Participants | 139 Participants |
| Sex: Female, Male Male | 191 Participants | 42 Participants | 149 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 96 / 99 | 287 / 288 |
| serious Total, serious adverse events | 48 / 99 | 146 / 288 |
Outcome results
Primary
Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)
Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.
Time frame: 2 years
Population: All imatinib-resistant participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR) | 159 Participants |
Secondary
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Blood samples were collected for PK to be included in separate population PK analyses.
Time frame: Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.
Population: No study-specific PK analyses were planned for this report.
Secondary
Median Time From First Dosing Date to Date of MCyR
MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Time frame: Baseline (within 4 weeks of Day 1) and every 12 weeks
Population: Population is limited to responders (those who acheived MCyR) only
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Median Time From First Dosing Date to Date of MCyR | Imatinib-intolerant | 2.79 Months |
| Dasatinib, 70 mg, Twice Daily (BID) | Median Time From First Dosing Date to Date of MCyR | Imatinib-resistant | 2.92 Months |
Secondary
Median Time From First Dosing Until CHR
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Time frame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Population: Population limited to responders (those achieving CHR) only
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Median Time From First Dosing Until CHR | Imatinib-resistant (n=259) | 0.53 Months |
| Dasatinib, 70 mg, Twice Daily (BID) | Median Time From First Dosing Until CHR | Imatinib-intolerant (n=93) | 0.49 Months |
Secondary
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.
Time frame: Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.
Population: Number of participants with assessments at baseline and timepoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-intolerant: Total FACT-G (n=80) | 34 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-intolerant: EWB (n=80) | 40 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-intolerant: FWB (n=80) | 32 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-resistant: Total FACT-G (n=241) | 107 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-resistant: PWB (n=241) | 103 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-resistant: SWB (n=241) | 94 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-intolerant: PWB (n=80) | 36 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-intolerant: SWB (n=80) | 33 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-resistant: EWB (n=241) | 107 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores | Imatinib-resistant: FWB (n=241) | 89 Participants |
Secondary
Number of Imatinib-intolerant Participants With MCyR
Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Time frame: Baseline to 2 years
Population: All imatinib-intolerant participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imatinib-intolerant Participants With MCyR | 81 Participants |
Secondary
Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Time frame: Continuously, from baseline through 2 years
Population: All imitanib-intolerant participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Drug-related AEs | 97 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Death within 30 days of last dose | 0 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Deaths | 0 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | On-study AEs leading to discontinuation | 16 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | SAEs | 48 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Grade 3-4 thrombocytopenia | 32 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Grade 3-4 neutropenia | 39 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE | Any AE | 98 Participants |
Secondary
Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Time frame: Continuously, from baseline through 2 years
Population: All imitanib-resistant participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Death within 30 days of last dose | 8 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Deaths | 19 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | On-study AEs leading to Discontinuation | 53 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Grade 3-4 thrombocytopenia | 156 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Grade 3-4 neutropenia | 154 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Any AE | 288 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | Drug-related AEs | 281 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE | SAEs | 146 Participants |
Secondary
Number of Participants With Complete Hematologic Response (CHR)
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Time frame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Population: All participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Participants With Complete Hematologic Response (CHR) | Imatinib-intolerant (n=99) | 93 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Participants With Complete Hematologic Response (CHR) | Imatinib-resistant (n=288) | 259 Participants |
Secondary
Number of Participants With Major Molecular Response (MMR)
MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor.
Time frame: Baseline to 2 years
Population: All participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Participants With Major Molecular Response (MMR) | Imatinib-intolerant (n=99) | 73 Participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Number of Participants With Major Molecular Response (MMR) | Imatinib-resistant (n=288) | 102 Participants |
Secondary
Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months
Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Time frame: 12 and 24 months
Population: Population limited to responders (those achieving CHR) only
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months | Imatinib-intolerant: 12 months (n=93) | 97.7 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months | Imatinib-intolerant: 24 months (n=93) | 93.5 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months | Imatinib-resistant: 12 months (n=259) | 90.4 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months | Imatinib-resistant: 24 months (n=259) | 78.8 Percentage of participants |
Secondary
Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months
Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.
Time frame: 12 and 24 Months
Population: Population is limited to responders (those who acheived MCyR) who were also assessed for duration of MCyR.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months | Imatinib-intolerant group: 12 months (n=81) | 98.5 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months | Imatinib-intolerant group: 24 months (n=81) | 96.7 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months | Imatinib-resistant group: 12 months (n=159) | 93.7 Percentage of participants |
| Dasatinib, 70 mg, Twice Daily (BID) | Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months | Imatinib-resistant group: 24 months (n=159) | 83.6 Percentage of participants |