Trial Outcomes & Findings for Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia (NCT NCT00101647)

Last Updated: 2011-04-15

Results Overview

MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). OHR=best confirmed response of MaHR or minor hematologic response (MiHR). Confirmed hematologic response=response confirmed ≥4 weeks after first documented event with no concomitant use of anagrelide or hydroxyurea. Maintaining a response=no 2 consecutive records of nonresponse at assessment. Criteria for CHR and NEL specified in Outcome Measure 2 and criteria for MiHR in Outcome Measure 4.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

197 participants

Primary outcome timeframe

Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Results posted on

2011-04-15

Participant Flow

197 participants were enrolled into the study; 23 participants were not treated (3 participants died, 13 participants no longer met study criteria, 3 participants switched into other studies, 2 participants had adverse events, 1 participant excluded for administrative reasons, and 1 participant withdrew consent).

Participant milestones

Participant milestones
Measure	Imatinib-intolerant Defined as either: i) toxicity that was considered at least possibly related to imatinib ≤ 400 mg/day that led to a discontinuation of imatinib therapy; ii) ability to tolerate only \< 400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses, was not considered imatinib-tolerant.	Imatinib-resistant Defined as any of the following: i) initial diagnosis of chronic phase of chronic myeloid leukemia (CML) that progressed to accelerated phase while on treatment with imatinib ≥ 400 mg/day (primary or acquired resistance); ii) initial diagnosis of accelerated phase CML and failure to achieve a hematologic response after ≥ 4 weeks (or ≥ 2 weeks for subjects showing rapid disease progression) of imatinib ≥ 600 mg/day; the required prior imatinib dose was 400 to \< 600 mg/day if the subject was intolerant to ≥ 600 mg/day (primary resistance); iii) initial diagnosis of accelerated or blast phase CML that progressed to accelerated phase CML following an initial hematologic response to imatinib ≥ 600 mg/day (acquired resistance). The required prior imatinib dose was 400 to \< 600 mg/day if the subject was intolerant of ≥ 600 mg/day.
Overall Study STARTED	13	161
Overall Study COMPLETED	13	161
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Dasatinib (BMS-354825) in Patients With Accelerated Phase Chronic Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Imatinib-intolerant n=13 Participants Defined as either: i) toxicity that was considered at least possibly related to imatinib ≤ 400 mg/day that led to a discontinuation of imatinib therapy; ii) ability to tolerate only \< 400 mg/day imatinib. A subject who tolerated 400 mg/day imatinib, but was intolerant of higher doses, was not considered imatinib-tolerant.	Imatinib-resistant n=161 Participants Defined as any of the following: i) initial diagnosis of chronic phase of chronic myeloid leukemia (CML) that progressed to accelerated phase while on treatment with imatinib ≥ 400 mg/day (primary or acquired resistance); ii) initial diagnosis of accelerated phase CML and failure to achieve a hematologic response after ≥ 4 weeks (or ≥ 2 weeks for subjects showing rapid disease progression) of imatinib ≥ 600 mg/day; the required prior imatinib dose was 400 to \< 600 mg/day if the subject was intolerant to ≥ 600 mg/day (primary resistance); iii) initial diagnosis of accelerated or blast phase CML that progressed to accelerated phase CML following an initial hematologic response to imatinib ≥ 600 mg/day (acquired resistance). The required prior imatinib dose was 400 to \< 600 mg/day if the subject was intolerant of ≥ 600 mg/day.	Total n=174 Participants Total of all reporting groups
Age, Customized 21 to 45 years	2 participants n=99 Participants	41 participants n=107 Participants	43 participants n=206 Participants
Age, Customized 46 to 65 years	6 participants n=99 Participants	87 participants n=107 Participants	93 participants n=206 Participants
Age, Customized 66 to 75 years	4 participants n=99 Participants	25 participants n=107 Participants	29 participants n=206 Participants
Age, Customized >75 years	1 participants n=99 Participants	8 participants n=107 Participants	9 participants n=206 Participants
Age Continuous	58.4 years STANDARD_DEVIATION 14.2 • n=99 Participants	54.5 years STANDARD_DEVIATION 13.7 • n=107 Participants	54.8 years STANDARD_DEVIATION 13.7 • n=206 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	69 Participants n=107 Participants	78 Participants n=206 Participants
Sex: Female, Male Male	4 Participants n=99 Participants	92 Participants n=107 Participants	96 Participants n=206 Participants
Race/Ethnicity, Customized Asian	1 participants n=99 Participants	23 participants n=107 Participants	24 participants n=206 Participants
Race/Ethnicity, Customized Black or African American	1 participants n=99 Participants	8 participants n=107 Participants	9 participants n=206 Participants
Race/Ethnicity, Customized White	11 participants n=99 Participants	127 participants n=107 Participants	138 participants n=206 Participants
Race/Ethnicity, Customized Other	0 participants n=99 Participants	3 participants n=107 Participants	3 participants n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=0 fully active	6 units on a scale n=99 Participants	73 units on a scale n=107 Participants	79 units on a scale n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=1 physically strenuous activity restricted	4 units on a scale n=99 Participants	67 units on a scale n=107 Participants	71 units on a scale n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=2 capable of all selfcare, unable to work	3 units on a scale n=99 Participants	21 units on a scale n=107 Participants	24 units on a scale n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=3 limited selfcare, bed/chair confined >50%	0 units on a scale n=99 Participants	0 units on a scale n=107 Participants	0 units on a scale n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=4 completely disabled, bed/chair confined	0 units on a scale n=99 Participants	0 units on a scale n=107 Participants	0 units on a scale n=206 Participants
Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) score=5 dead	0 units on a scale n=99 Participants	0 units on a scale n=107 Participants	0 units on a scale n=206 Participants
Functional Assessment of Cancer Therapy-General (FACT-G) Total FACT-G	81.9 units on a scale STANDARD_DEVIATION 14.4 • n=99 Participants	75.3 units on a scale STANDARD_DEVIATION 18.0 • n=107 Participants	75.8 units on a scale STANDARD_DEVIATION 17.8 • n=206 Participants
Functional Assessment of Cancer Therapy-General (FACT-G) Physical Well Being	22.3 units on a scale STANDARD_DEVIATION 5.2 • n=99 Participants	19.0 units on a scale STANDARD_DEVIATION 7.1 • n=107 Participants	19.2 units on a scale STANDARD_DEVIATION 7.0 • n=206 Participants
Functional Assessment of Cancer Therapy-General (FACT-G) Social/Family Well-Being	22.8 units on a scale STANDARD_DEVIATION 5.1 • n=99 Participants	22.7 units on a scale STANDARD_DEVIATION 4.8 • n=107 Participants	22.7 units on a scale STANDARD_DEVIATION 4.8 • n=206 Participants
Functional Assessment of Cancer Therapy-General (FACT-G) Emotional Well-Being	17.7 units on a scale STANDARD_DEVIATION 4.8 • n=99 Participants	16.7 units on a scale STANDARD_DEVIATION 4.9 • n=107 Participants	16.8 units on a scale STANDARD_DEVIATION 4.9 • n=206 Participants
Functional Assessment of Cancer Therapy-General (FACT-G) Functional Well-Being	19.2 units on a scale STANDARD_DEVIATION 6.9 • n=99 Participants	16.9 units on a scale STANDARD_DEVIATION 6.7 • n=107 Participants	17.1 units on a scale STANDARD_DEVIATION 6.8 • n=206 Participants

PRIMARY outcome

Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Population: All treated subjects

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=13 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=161 Participants Receiving dasatinib 70 mg BID	Total n=174 Participants
Major and Overall Hematologic Response (MaHR and OHR) MaHR	9 participants	103 participants	112 participants
Major and Overall Hematologic Response (MaHR and OHR) OHR	12 participants	127 participants	139 participants

SECONDARY outcome

Timeframe: 12 months

Population: Population comprised of responders only.

MaHR=best response of CHR or NEL. CHR=white blood cells ≤institutional upper limit of normal (iULN); absolute neutrophil count (ANC) ≥1000/mm3; platelets ≥100,000/mm3; no blasts/promyelocytes in peripheral blood (PB); bone marrow blasts ≤5%; \<5% myelocytes+metamyelocytes in PB; PB basophils ≤ iULN; no extramedullary involvement. NEL=WBC ≤iULN; no blasts/promyelocytes in PB; bone marrow blasts ≤5%; \<5% myelocytes+metamyelocytes in PB; PB basophils ≤iULN; no extramedullary involvement; at least 1 of: ANC ≥500/mm3 \& \<1000/mm3; platelets ≥20,000/mm3 \& \<100,000/mm3.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=9 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=103 Participants Receiving dasatinib 70 mg BID	Total n=112 Participants
Percentage of Participants Who Achieved MaHR and Did Not Progress at 12 Months (Based on the Kaplan-Meier Estimate of the Duration of Response)	85.7 percentage of responders	78.3 percentage of responders	79.0 percentage of responders

SECONDARY outcome

Timeframe: 24 months

Population: Population comprised of responders only. NOTE: Projected duration of MaHR at 24 months in the Imatinib-Intolerant group was beyond the maximum observed time for this cohort, and therefore only the Imatinib-Resistant group is presented.

Percentage of participants in the Imatinib-Resistant Group who achieved MaHR and did not progress at Month 24, based on the Kaplan-Meier estimate of the duration of response. MaHR=best confirmed response of complete hematologic response (CHR) or No Evidence of Leukemia (NEL). Criteria for MaHR and NEL are specified in Outcome Measure 2.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=161 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=161 Participants Receiving dasatinib 70 mg BID	Total
Percentage of Participants Who Achieved MaHR and Did Not Progress at 24 Months in the Imatinib-Resistant Group (Based on the Kaplan-Meier Estimate of the Duration of Response)	60.9 percentage of responders	59.6 percentage of responders	—

SECONDARY outcome

Timeframe: 12 months, 24 months

Population: Population is comprised of responders only

Percentage of participants who achieved OHR and did not progress at specified timepoints, based on the Kaplan-Meier estimate of the duration of response. OHR=best confirmed response of MaHR or MiHR. MaHR criteria in Outcome Measure 2. MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts+promyelocytes in bone marrow and \<30% blasts+promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response= confirmed ≥4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=12 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=127 Participants Receiving dasatinib 70 mg BID	Total n=139 Participants
Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months OHR at 12 months	69.8 Percentage of responders	69.7 Percentage of responders	69.8 Percentage of responders
Percentage of Participants Who Achieved OHR and Did Not Progress at 12 Months and 24 Months OHR at 24 months	34.9 Percentage of responders	51.2 Percentage of responders	50.0 Percentage of responders

SECONDARY outcome

Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Population: Population is comprised of responders only

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=9 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=103 Participants Receiving dasatinib 70 mg BID	Total n=112 Participants
Median Time in Days From First Dosing Date to Date of MaHR	84 Days Interval 28.0 to 148.0	63 Days Interval 26.0 to 420.0	65 Days Interval 26.0 to 420.0

SECONDARY outcome

Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Population: Population comprised of responders only

Median time (in months) from first dosing date to date of OHR. OHR=best confirmed response of MaHR or MiHR. Criteria for MaHR specified in Outcome Measure 2. MiHR= \<15% blasts in bone marrow and \<15% blasts in peripheral blood (PB); \<30% blasts+promyelocytes in bone marrow and \<30% blasts+promyelocytes in PB; \<20% basophils in PB; no extramedullary disease other than spleen and liver. Confirmed hematologic response = response confirmed ≥4 weeks after 1st documented event with no concomitant use of anagrelide or hydroxyurea.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=12 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=127 Participants Receiving dasatinib 70 mg BID	Total n=139 Participants
Time to OHR	34 days Interval 28.0 to 92.0	30 days Interval 17.0 to 420.0	30 days Interval 17.0 to 420.0

SECONDARY outcome

Timeframe: Baseline (within 4 weeks of therapy start); Every month for Cycles 1-3; Every 12 weeks for Cycles 4+; end of treatment

Population: All treated subjects

Number of participants with complete, partial, minor, minimal, or no cytogenetic response. Determination of cytogenetic response based on the prevalence (percentage) of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase in a bone marrow sample (aspirates/biopsies).

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=13 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=161 Participants Receiving dasatinib 70 mg BID	Total n=174 Participants
Best Cytogenetic Response Complete (0% Ph+ metaphases)	5 Participants	53 Participants	58 Participants
Best Cytogenetic Response Partial (>0% to 35% Ph+ metaphases)	0 Participants	12 Participants	12 Participants
Best Cytogenetic Response Minor (>35% to 65% Ph+ metaphases)	0 Participants	8 Participants	8 Participants
Best Cytogenetic Response Minimal (>65% to 95% Ph+ metaphases)	3 Participants	37 Participants	40 Participants
Best Cytogenetic Response No Response (>95% to 100% Ph+ metaphases)	4 Participants	37 Participants	41 Participants
Best Cytogenetic Response Unable to determine	1 Participants	14 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline (within 72 hours of therapy start); Cycle 1/Day 1; Weekly during treatment; at end of treatment

Population: All treated subjects

Number of participants with confirmed complete hematologic response (CHR) or No Evidence of Leukemia (NEL), minor hematologic response (MiHR), or no hematologic response. Confirmed hematologic response=response that is confirmed after at least 4 weeks with no concomitant use of anagrelide or hydroxyurea use during this interval. Criteria for CHR and NEL are specified in Outcome Measure 2; criteria for MiHR are specified in Outcome Measure 4.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=13 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=161 Participants Receiving dasatinib 70 mg BID	Total n=174 Participants
Best Confirmed Hematologic Response Complete HR (CHR)	7 Participants	80 Participants	87 Participants
Best Confirmed Hematologic Response No Evidence of Leukemia (NEL)	2 Participants	23 Participants	25 Participants
Best Confirmed Hematologic Response Minor HR (MiHR)	3 Participants	24 Participants	27 Participants
Best Confirmed Hematologic Response No Response	1 Participants	34 Participants	35 Participants

SECONDARY outcome

Timeframe: Baseline, every 12 weeks throughout study (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).

Population: Number of Participants Analyzed=all treated subjects who were assessed for major molecular response; n=participants with or without CCyR in cohort.

Number of participants who achieved an MMR at any time during the treatment period. MMR was calculated by measuring BCR-ABL transcripts in blood during treatment using quantitative reverse transcription-polymerase chain reaction (RT-PCR). BCR-ABL=the fused gene found in subjects with this type of Chronic Myeloid Leukemia (CML).

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=4 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=90 Participants Receiving dasatinib 70 mg BID	Total n=94 Participants
Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period MMR in Assessed Participants w/CCyR(n=2;n=39;n=41)	2 participants	17 participants	19 participants
Number of Participants Who Achieved a Major Molecular Response (MMR) During Treatment Period MMR in Assessed Subjects w/o CCyR(n=2;n=51;n=53)	0 participants	11 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, at time of disease progression. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).

Population: All subjects with baseline mutation data; n=the number of participants with the specified mutation. Baseline mutation data were reported for 162 of the 174 subjects (12/13 imatinib-intolerant and 150/161 imatinib-resistant). At baseline, 89 (59%) imatinib-resistant subjects and 1 imatinib-intolerant subject expressed imatinib resistant mutations.

Major hematologic and cytogenetic responses (MaHR and MCyR) to dasatinib in subjects with mutations at baseline, including imatinib-resistant mutations (IRM) and specific BCR-ABL mutations (SBAM). BCR-ABL=the fused gene found in subjects with this type of CML. Criteria for MaHR are specified in Outcome Measure 2. MCyR=combined complete cytogenetic and partial cytogenetic response rate. Complete Cytogenetic Response= 0% Ph+ Cells in Metaphase in Bone Marrow, Partial Cytogenetic Response \> 0% to 35% Ph+ Cells in Metaphase in Bone Marrow.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=162 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=162 Participants Receiving dasatinib 70 mg BID	Total
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations with ≥1 IRM in P-loop (n=35)	69 Percentage of participants	31 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [F359C/I/V] at baseline (n=12)	83 Percentage of participants	42 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [H396R] at baseline (n=6)	67 Percentage of participants	33 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [V379I] at baseline (n=6)	67 Percentage of participants	67 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [E355G] at baseline (n=4)	50 Percentage of participants	50 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations Participants with IRM (n=90)	73 Percentage of participants	40 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations with ≥1 IRM in activation loop (n=15)	73 Percentage of participants	53 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations with ≥1 IRM in P-loop & activation loop (n=3)	33 Percentage of participants	67 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations with ≥1 IRM in other location only (n=43)	74 Percentage of participants	44 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations w/ ≥1 IRM w/2-4-fold increase in IR (n=15)	87 Percentage of participants	33 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations w/ ≥1 IMR w/≥5-fold increase in IR (n=60)	67 Percentage of participants	35 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [M244V] at baseline (n=7)	86 Percentage of participants	71 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [L248V] at baseline (n=3)	100 Percentage of participants	67 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [G250E] at baseline (n=10)	60 Percentage of participants	20 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [Y253F/H] at baseline (n=11)	82 Percentage of participants	45 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [E255K/V] at baseline (n=11)	64 Percentage of participants	18 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [T315I] at baseline (n=9)	0 Percentage of participants	0 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [F317L] at baseline (n=4)	100 Percentage of participants	0 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [M351T/V] at baseline (n=13)	85 Percentage of participants	38 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [S417Y] at baseline (n=3)	33 Percentage of participants	0 Percentage of participants	—
MaHR and MCyR Among Participants With Baseline BCR-ABL Point Mutations SBAM [E459K] at baseline (n=3)	33 Percentage of participants	100 Percentage of participants	—

SECONDARY outcome

Timeframe: Baseline, every 2 weeks for the first 3 cycles, following every 4-week cycle, and once at follow-up.(treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).

Population: Number of participants with FACT-G assessments at baseline and at least one assessment during treatment

Number of subjects with minimally significant changes from baseline in the health-related quality of life questionnaire FACT-G. FACT-G=27 questions in 4 domains: physical, social/family, emotional, and functional well-being (PWB, SWB, EWB, FWB). Total score=0 to 108; higher score=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, and FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinically important change.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=12 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=134 Participants Receiving dasatinib 70 mg BID	Total n=146 Participants
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Social/Family Well-Being	6 Participants	50 Participants	56 Participants
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Emotional Well-Being	7 Participants	77 Participants	84 Participants
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total FACT-G	5 Participants	76 Participants	81 Participants
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Physical Well-Being	4 Participants	85 Participants	89 Participants
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Functional Well-Being	4 Participants	63 Participants	67 Participants

SECONDARY outcome

Timeframe: Continuous from pretreatment through each 4-week cycle and at follow-up. (treatment continued until discontinuation due to toxicity, disease progression, or other protocol-specified criteria).

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)

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=13 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=161 Participants Receiving dasatinib 70 mg BID	Total
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Fluid-Retention AEs -Overall	10 Participants	104 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Fluid-Retention AEs - Other	4 Participants	43 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Grade 3/4 Hematologic Toxicity - Anemia	11 Participants	111 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Any AE	13 Participants	160 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Grade 3/4 AEs	12 Participants	116 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Drug-Related AEs	13 Participants	155 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Drug-Related Grade 3-4 AEs	11 Participants	95 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Death within 30 days of last dose	2 Participants	15 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation SAEs	12 Participants	113 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Fluid-Retention AEs - Superficial Edema	8 Participants	73 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Fluid-Retention AEs -Pleural Effusion	4 Participants	60 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Grade 3/4 Hematologic Toxicity - Thrombocytopenia	10 Participants	132 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Grade 3/4 Hematologic Toxicity - Neutropenia	13 Participants	120 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Grade 3/4 Hematologic Toxicity - Leukopenia	11 Participants	91 Participants	—
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths, Hematologic Toxicities, and Toxicities Leading to Discontinuation Discontinuations due to Study Drug Toxicity	2 Participants	19 Participants	—

SECONDARY outcome

Timeframe: Collected on Days 1 and 8 at times as close as possible to the following time points (relative to drug administration): pre-dose, and following drug administration at 30 minutes, 1 hour, 1.5, 2, 3, 4, 5, 6, 8 and 10 hours.

Population: 29 participants had dense PK sampling on Day 1 and Day 8; parameters for 2 participants on Day 8 were excluded due to unreliable data. Participants with all concentration-time values \< than the limit of quantitation were treated as missing for PK analysis. n= participants included in the statistical analyses of PK on Day 1 and Day 8, respectively.

The Cmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=29 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=27 Participants Receiving dasatinib 70 mg BID	Total
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax) Dasatinib (n=29; n=27)	69.31 ng/mL Standard Deviation 43.08	89.18 ng/mL Standard Deviation 68.38	—
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Maximum Observed Plasma Concentration (Cmax) BMS-582691 (n=24; n=24)	2.81 ng/mL Standard Deviation 1.53	4.52 ng/mL Standard Deviation 3.04	—

SECONDARY outcome

The AUC(0-T) was calculated using the mixed log-linear trapezoidal algorithm in Kinetica™. In the calculation of AUC(0-T), predose concentrations that were less than the lower limit of quantitation (LLQ) were assigned a value of zero.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=29 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=27 Participants Receiving dasatinib 70 mg BID	Total
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 Hours (AUC[0-T]) Dasatinib (n=29; n=27)	207.76 ng∙h/mL Standard Deviation 126.05	265.02 ng∙h/mL Standard Deviation 184.73	—
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point Within the Dosing Interval of 12 Hours (AUC[0-T]) BMS-582691 (n=24; n=24)	9.51 ng∙h/mL Standard Deviation 8.11	18.67 ng∙h/mL Standard Deviation 15.58	—

SECONDARY outcome

Population: A total of 29 participants had dense PK sampling on both Day 1 and Day 8; parameters for 2 participants on Day 8 were excluded due to unreliable concentration-time profiles. n=the number of participants on Day 1 and Day 8 who were included in the statistical analyses of PK parameters.

The Tmax was obtained from experimental observations. Using no weighting factor, the terminal log-linear phase of the concentration-time curve was identified by least-square linear regression of at least 3 data points that yielded a maximum G-criteria,which is also referred to as adjusted R-squared.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=29 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=27 Participants Receiving dasatinib 70 mg BID	Total
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax) Dasatinib (n=29; n=27)	1.26 hours Standard Deviation 0.98 • Interval 0.42 to 5.0	1.13 hours Standard Deviation 0.93 • Interval 0.5 to 4.75	—
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Time to Maximum Observed Plasma Concentration (Tmax) BMS-582691 (n=24; n=24)	1.86 hours Standard Deviation 0.88 • Interval 0.5 to 4.32	1.75 hours Standard Deviation 1.12 • Interval 0.25 to 5.57	—

SECONDARY outcome

The T-HALF was calculated as Ln2/Lz,where Lz was the absolute value of the slope of the terminal log-linear phase.

Outcome measures

Outcome measures
Measure	Imatinib-intolerant n=29 Participants Receiving dasatinib 70 mg twice daily (BID)	Imatinib-resistant n=27 Participants Receiving dasatinib 70 mg BID	Total
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF) Dasatinib (n=28; n=26)	3.15 hours Standard Deviation 0.86	5.18 hours Standard Deviation 2.12	—
Pharmacokinetics (PK) of Dasatinib and Its Metabolite BMS-582691 - Plasma Half-life (T-HALF) BMS-582691 (n=22; n=20)	3.30 hours Standard Deviation 1.94	5.70 hours Standard Deviation 4.89	—

SECONDARY outcome

Timeframe: Day 8 immediately prior to the first daily dose and between 30 minutes to 3 hours following this dose.

Population pharmacokinetic analysis was not done because it is not meaningful for this single study

Outcome measures

Outcome data not reported

Adverse Events

Intolerant

Serious events: 12 serious events

Other events: 13 other events

Deaths: 0 deaths

Resistant

Serious events: 113 serious events

Other events: 158 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER