Chronic Myeloid Leukemia, Philadelphia-Positive Myeloid Leukemia
Conditions
Keywords
Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia
Brief summary
The primary purpose of this study is to estimate the major cytogenetic response rates of BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of 400-600 mg/d.
Interventions
DRUGDasatinib
Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks
DRUGImatinib
Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women, 18 years of age or older. * Subjects with Chronic Phase Ph+ CML. * Subjects have not been treated with imatinib at a dose \>600 mg/day. * Subjects developed resistance to disease while receiving an imatinib dose 400-600 mg/day. * Able to tolerate imatinib at the highest dose the subject had received in the past. * Demonstrate adequate renal and hepatic function. * Women of childbearing potential must have a negative serum or urine pregnancy test, must be using an adequate method of contraception.
Exclusion criteria
* Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period for a least 1 month before and at least 3 months after the completion of the study. * Women using a prohibited contraceptive method. * Women 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. * Prior treatment with imatinib at a dose \>600 mg/day. * Subjects who have previously identified specific BCR-ABL mutations. * Previous diagnosis of accelerated phase or blast crisis CML. * Intolerance to imatinib at any dose. * Subjects who are eligible and willing to undergo transplantation during the screening period. * Serious uncontrolled medical disorder or active infection. * Uncontrolled or significant cardiovascular disease. * Uncontrolled hypertension. * Dementia or altered mental status. * Evidence of organ dysfunction. * 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. * Subjects taking certain medications that are accepted to have a risk of causing Torsades de Pointes. * Subjects taking medications that irreversibly inhibit platelet function or anticoagulants. * Prior therapy with BMS-354825.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Cytogenetic Response (MCyR) at Week 12 | Week 12 | Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; \>0% to 35% Ph+ cells in metaphase in bone marrow). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of MCyR at 12 Months and 18 Months | 12 months, 18 months | Percentage of participants who achieved MCyR and did not progress at 12 and 18 months. |
| Duration of MCyR at 24 Months | 24 Months | Percentage of participants who achieved MCyR and did not progress at 24 months. |
| Time to MCyR Prior to Crossover | Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements. | Median time from first dosing date to date of MCyR |
| Complete Hematologic Response (CHR) at Any Time Prior to Crossover | Baseline (within 4 weeks of Day 1), weekly until Week 12 and then every 12 weeks until crossover or off-study; restricted to precrossover measurements. | Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response. |
| Duration of Complete Hematologic Response (CHR) | 12 months, 24 months | Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response. |
| Time to CHR Prior to Crossover | Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements. | Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response. |
| MCyR at Any Time Prior to Crossover | Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements. | Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (\>0% to 35% Ph+ cells in metaphase in bone marrow). |
| CHR After Crossover | Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements. | Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response. |
| Cytogenetic Response After Crossover | every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements | Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (\>0% to 35% Ph+ cells in metaphase in bone marrow). |
| Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Continuously from baseline through 2 years | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death) |
| Health-Related Quality of Life Prior to Crossover | Every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment. Last questionnaire was to be completed at first follow-up visit after off-study date. | Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, & SWB score change of 2 or more=minimal clinical important change. |
| Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib | Day 8: pretreatment trough sample, a sample between 30 minutes and 3 hours following treatment, a sample between 5 and 8 hours following treatment, and a sample at 12 hours, prior to the next dose. | Number of participants from which blood samples were collected for population PK studies. |
| Major Molecular Response (MMR) | Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements. | Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, Estonia, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Norway, Peru, Philippines, Poland, Puerto Rico, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
Participant flow
Pre-assignment details
166 subjects enrolled; 16 failed screening and were not treated (2 subjects were double-randomizations, 13 subjects failed inclusion criteria, 1 subject withdrew consent during screening.)
Participants by arm
| Arm | Count |
|---|---|
| Dasatinib Dasatinib 70 mg twice a day (BID) | 101 |
| Imatinib Imatinib 400 mg BID | 49 |
| Total | 150 |
Baseline characteristics
| Characteristic | Total | Imatinib | Dasatinib |
|---|---|---|---|
| Age Continuous | 51 years STANDARD_DEVIATION 13.6 | 50 years STANDARD_DEVIATION 13.6 | 51 years STANDARD_DEVIATION 13.6 |
| Age, Customized >75 years | 5 participants | 1 participants | 4 participants |
| Age, Customized Between 21 and 45 years | 51 participants | 15 participants | 36 participants |
| Age, Customized Between 46 and 65 years | 76 participants | 28 participants | 48 participants |
| Age, Customized Between 66 and 75 years | 18 participants | 5 participants | 13 participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Not Reported | 6 Participants | 3 Participants | 3 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=0 (fully active) | 105 Participants | 34 Participants | 71 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=1 (ambulatory, light/sedentary work) | 39 Participants | 12 Participants | 27 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=2 (ambulatory, all selfcare, unable to work) | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=3 (limited selfcare, some bed confinement) | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=4 (completely disabled) | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) Score=5 (dead) | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 8 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 130 Participants | 43 Participants | 87 Participants |
| Sex: Female, Male Female | 75 Participants | 27 Participants | 48 Participants |
| Sex: Female, Male Male | 75 Participants | 22 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 99 / 101 | 43 / 49 |
| serious Total, serious adverse events | 43 / 101 | 4 / 49 |
Outcome results
Primary
Number of Participants With Major Cytogenetic Response (MCyR) at Week 12
Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; \>0% to 35% Ph+ cells in metaphase in bone marrow).
Time frame: Week 12
Population: All randomized subjects
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Number of Participants With Major Cytogenetic Response (MCyR) at Week 12 | 36 Participants |
| Imatinib | Number of Participants With Major Cytogenetic Response (MCyR) at Week 12 | 14 Participants |
Secondary
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover
AE=any new untoward medical occurrence or worsening of a pre-existing medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Time frame: Continuously from baseline through 2 years
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Overall | 39 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Any Adverse Event (AE) | 100 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Superficial Edema | 20 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Death within 30 days of last dose | 1 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Pleural Effusion | 25 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related AEs | 94 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Other | 9 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Anemia | 20 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related Serious AEs | 28 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Thrombocytopenia | 58 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 AEs | 67 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Neutropenia | 64 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | AEs leading to discontinuation | 23 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Leukopenia | 24 Participants |
| Dasatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related Grade 3-4 AEs | 62 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Leukopenia | 8 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Any Adverse Event (AE) | 45 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 AEs | 21 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related AEs | 44 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related Grade 3-4 AEs | 19 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Death within 30 days of last dose | 0 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Drug-related Serious AEs | 3 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | AEs leading to discontinuation | 10 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Overall | 21 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Superficial Edema | 21 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Pleural Effusion | 0 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Anemia | 4 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Thrombocytopenia | 7 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Grade 3-4 Hematologic Toxicity - Neutropenia | 19 Participants |
| Imatinib | Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover | Fluid Retention AEs - Other | 0 Participants |
Secondary
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Number of participants from which blood samples were collected for population PK studies.
Time frame: Day 8: pretreatment trough sample, a sample between 30 minutes and 3 hours following treatment, a sample between 5 and 8 hours following treatment, and a sample at 12 hours, prior to the next dose.
Population: Blood samples that were to contribute to PK modeling were collected from 78 participants,to be included in separate population PK analyses. Although blood sample collection was listed as a secondary endpoint, no study-specific PK analyses were planned for this report.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib | 78 participants |
Secondary
CHR After Crossover
Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time frame: Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.
Population: Participants evaluable for response after crossover
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | CHR After Crossover | 37 Participants |
| Imatinib | CHR After Crossover | 13 Participants |
Secondary
Complete Hematologic Response (CHR) at Any Time Prior to Crossover
Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time frame: Baseline (within 4 weeks of Day 1), weekly until Week 12 and then every 12 weeks until crossover or off-study; restricted to precrossover measurements.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Complete Hematologic Response (CHR) at Any Time Prior to Crossover | 94 Participants |
| Imatinib | Complete Hematologic Response (CHR) at Any Time Prior to Crossover | 40 Participants |
Secondary
Cytogenetic Response After Crossover
Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (\>0% to 35% Ph+ cells in metaphase in bone marrow).
Time frame: every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements
Population: Participants evaluable for after crossover response
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Cytogenetic Response After Crossover | Major Cytogenetic Response (MCyR) | 19 Participants |
| Dasatinib | Cytogenetic Response After Crossover | Complete Cytogenetic Response (CCyR) | 15 Participants |
| Dasatinib | Cytogenetic Response After Crossover | Partial Cytogenetic Response (PCyR) | 4 Participants |
| Imatinib | Cytogenetic Response After Crossover | Major Cytogenetic Response (MCyR) | 3 Participants |
| Imatinib | Cytogenetic Response After Crossover | Complete Cytogenetic Response (CCyR) | 0 Participants |
| Imatinib | Cytogenetic Response After Crossover | Partial Cytogenetic Response (PCyR) | 3 Participants |
Secondary
Duration of Complete Hematologic Response (CHR)
Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time frame: 12 months, 24 months
Population: Number of participants achieving CHR in each treatment group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Duration of Complete Hematologic Response (CHR) | 12 months | 92 percentage of participants |
| Dasatinib | Duration of Complete Hematologic Response (CHR) | 24 months | 84 percentage of participants |
| Imatinib | Duration of Complete Hematologic Response (CHR) | 12 months | 82 percentage of participants |
| Imatinib | Duration of Complete Hematologic Response (CHR) | 24 months | 73 percentage of participants |
Secondary
Duration of MCyR at 12 Months and 18 Months
Percentage of participants who achieved MCyR and did not progress at 12 and 18 months.
Time frame: 12 months, 18 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | Duration of MCyR at 12 Months and 18 Months | 12 months | 92 percentage of participants. |
| Dasatinib | Duration of MCyR at 12 Months and 18 Months | 18 months | 90 percentage of participants. |
| Imatinib | Duration of MCyR at 12 Months and 18 Months | 12 months | 74 percentage of participants. |
| Imatinib | Duration of MCyR at 12 Months and 18 Months | 18 months | 74 percentage of participants. |
Secondary
Duration of MCyR at 24 Months
Percentage of participants who achieved MCyR and did not progress at 24 months.
Time frame: 24 Months
Population: In the imatinib group, the 24 months timepoint was beyond the maximum observed time.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Duration of MCyR at 24 Months | 90 Percentage of Participants |
Secondary
Health-Related Quality of Life Prior to Crossover
Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, & SWB score change of 2 or more=minimal clinical important change.
Time frame: Every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment. Last questionnaire was to be completed at first follow-up visit after off-study date.
Population: Since single-arm quality-of-life data are not interpretable in a non-comparative trial, these data were not analyzed.
Secondary
Major Molecular Response (MMR)
Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), 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: Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.
Population: Participants assessed for MMR only
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dasatinib | Major Molecular Response (MMR) | 29 participants |
| Imatinib | Major Molecular Response (MMR) | 6 participants |
Secondary
MCyR at Any Time Prior to Crossover
Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (\>0% to 35% Ph+ cells in metaphase in bone marrow).
Time frame: Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dasatinib | MCyR at Any Time Prior to Crossover | MCyR (CCyR + PCyR) | 54 Participants |
| Dasatinib | MCyR at Any Time Prior to Crossover | CCyR (0% Ph+ cells) | 44 Participants |
| Dasatinib | MCyR at Any Time Prior to Crossover | PCyR (>0% to 35% Ph+ cells) | 10 Participants |
| Imatinib | MCyR at Any Time Prior to Crossover | MCyR (CCyR + PCyR) | 16 Participants |
| Imatinib | MCyR at Any Time Prior to Crossover | CCyR (0% Ph+ cells) | 9 Participants |
| Imatinib | MCyR at Any Time Prior to Crossover | PCyR (>0% to 35% Ph+ cells) | 7 Participants |
Secondary
Time to CHR Prior to Crossover
Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm³; no blasts or promyelocytes in peripheral blood; \< 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time frame: Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.
Population: Number of participants achieving CHR in each treatment group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib | Time to CHR Prior to Crossover | 2.1 weeks |
| Imatinib | Time to CHR Prior to Crossover | 2.1 weeks |
Secondary
Time to MCyR Prior to Crossover
Median time from first dosing date to date of MCyR
Time frame: Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.
Population: Population consists of the number of responders in each treatment group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dasatinib | Time to MCyR Prior to Crossover | 2.8 months |
| Imatinib | Time to MCyR Prior to Crossover | 2.8 months |