Trial Outcomes & Findings for Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma (NCT NCT00560352)

Last Updated: 2017-03-13

Results Overview

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended MTD is the maximum dose that the participants received.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Days 1 to 21

Results posted on

2017-03-13

Participant Flow

A total of 16 participants were enrolled, and 14 participants received treatment. The study was terminated due to an unexpectedly low recruitment rate, and no participants were enrolled in a planned dose-expansion phase.

Participant milestones

Participant milestones
Measure	Dasatinib, 50 mg BID Dasatinib, 50 mg administered twice daily (BID), with 1.0 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg once daily (QD), was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, BID. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Overall Study STARTED	7	3	4
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	7	3	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Dasatinib, 50 mg BID Dasatinib, 50 mg administered twice daily (BID), with 1.0 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg once daily (QD), was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, BID. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Overall Study Adverse event unrelated to study drug	2	1	1
Overall Study Study drug toxicity	3	0	1
Overall Study Disease progression	0	1	1
Overall Study Withdrawal by Subject	1	1	1
Overall Study Maximum clinical benefit	1	0	0

Baseline Characteristics

Safety Study of Dasatinib With Bortezomib (Velcade®) and Dexamethasone for Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dasatinib, 50 mg BID n=7 Participants Dasatinib, 50 mg administered twice daily (BID), with 1.0 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg once daily (QD), was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, BID. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 100 mg QD n=3 Participants Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD n=4 Participants Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Total n=14 Participants Total of all reporting groups
Age, Continuous	72 Years n=5 Participants	74 Years n=7 Participants	59.5 Years n=5 Participants	71 Years n=4 Participants
Age, Customized 46 to 65 years	1 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants
Age, Customized 66 to 75 years	6 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	9 Participants n=4 Participants
Age, Customized Older than 75 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized White	6 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Days 1 to 21

Population: All participants who received at least 1 dose of dasatinib and/or bortezomib and/or dexamethasone

Outcome measures

Outcome measures
Measure	All Treated n=14 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone MTD dasatinib	NA mg QD The MTD was not reached at the highest dose level defined by protocol for this study.	—	—
Maximum Tolerated Dose (MTD) and Recommended MTD of Dasatinib in Combination With Bortezomib and Dexamethasone Recommended MTD dasatinib	140 mg QD	—	—

PRIMARY outcome

Timeframe: Days 1 to 21

Population: All participants who received at least 1 dose of dasatinib and/or bortezomib and/or dexamethasone

MTD is defined as the dose level combination below the dose level that produces a dose-limiting toxicity in at least 2 out of 6 or fewer participants in that cohort. If MTD is not reached, the recommended dose is the maximum dose that the participants received.

Outcome measures

Outcome measures
Measure	All Treated n=14 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone MTD of bortezomib	NA mg/m^2 The MTD was not reached at the highest dose level defined by protocol for this study.	—	—
MTD and Recommended MTD of Bortezomib in Combination With Dasatinib and Dexamethasone Recommended MTD of bortezomib	1.3 mg/m^2	—	—

SECONDARY outcome

Timeframe: Day 1 until last tumor assessment (maximum reached: 9 months)

Population: All response-evaluable participants who received at least 1 dose of dasatinib and/or bortezomib and/or dexamethasone

S=serum; U=urine; MP=M-protein; ST=soft tissue, PC=plasmacytomas; IF=immunofixation; BL=baseline. RR calculated on best response any time. CR=MP undetectable by IF, ≤5% plasma cells in bone marrow, and no ST PC. VGPR=MP detectable by IF, or ≥90% drop in S MP and U MP\<100 mg/24h. PR= ≥50% drop in S MP and ≥90% drop in U MP or U protein \<200 mg/24h, ≥50% drop in BL ST PC size. MR= ≥25% to \<50% drop in S MP and ≥50% to \<90% drop in U MP and ≥25% to \<50% drop in BL ST PC. SD=Not CR, VGPR, PR, or MR. PD= ≥25% rise in S or U M-component; new/increased size of bone lesions, ST PC, or hypercalcemia.

Outcome measures

Outcome measures
Measure	All Treated n=7 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD n=3 Participants Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD n=4 Participants Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Complete response (CR)	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Very good partial response (VGPR)	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Partial response (PR)	14.3 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Minimal response (MR)	0 Percentage of participants	0 Percentage of participants	25 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Stable disease (SD)	57.1 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Progressive disease (PD)	14.3 Percentage of participants	33.3 Percentage of participants	0 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Unable to determine	0 Percentage of participants	33.3 Percentage of participants	25 Percentage of participants
Best Overall Tumor Response Rate (RR) As Assessed Using International Uniform Response Criteria for Multiple Myeloma and Criteria of the European Bone Marrow Transplant Registry Not reported	14.3 Percentage of participants	33.3 Percentage of participants	50 Percentage of participants

SECONDARY outcome

Timeframe: First occurrence of response to disease progression or death, whichever occurred first (maximum reached: 12.2 months)

Population: All response-evaluable participants who achieved a response.

Duration of response calculated for those with best response=CR (M-protein \[MP\] undetectable by immunofixation \[IF\], ≤5% plasma cells in bone marrow, no soft tissue plasmacytomas); VGPR (MP detectable by IF, or ≥90% drop in serum \[S\] MP and urine \[U\] MP\<100 mg/24h); PR(≥50% drop in S MP and ≥90% drop in U MP or U protein \<200 mg/24h, ≥50% drop in BL ST PC size); or MR (≥25% to \<50% drop in S MP and ≥50% to \<90% drop in U MP and ≥25% to \<50% drop in BL ST PC). Duration of response calculated from day criteria for CR, VGPR, PR, and MR were met until progression or death, whichever came first.

Outcome measures

Outcome measures
Measure	All Treated n=1 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD n=1 Participants Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Duration of Response Partial response (PR)	5.4 Months	—	0 Months
Duration of Response Minimal response (MR)	NA Months There were 0 participants who received 50 mg BID of dasatanib who had a minimal response.	—	12.2 Months

SECONDARY outcome

Timeframe: Day 1 to disease progression or death, whichever came first (maximum reached: 14 months)

Population: All participants who received at least 1 dose of dasatinib and/or bortezomib and/or dexamethasone

Progression-free survival was defined as the time from start of treatment until progression or death, whichever occurred first. Participants were to be followed-up for 12 months following the last dose of dasatinib for progression and survival. PFS was analyzed for the all-treated population.

Outcome measures

Outcome measures
Measure	All Treated n=14 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Progression-free Survival	6.3 Months Interval 2.4 to 14.0	—	—

SECONDARY outcome

Timeframe: Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)

Population: All participants who received at least 1 dose of dasatinib and/or bortezomib and/or dexamethasone.

An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=possibly, probably, or certainly related to or of unknown relationship to study treatment. Grade 3=severe; Grade 4=life-threatening.

Outcome measures

Outcome measures
Measure	All Treated n=7 Participants Dasatinib taken orally every day, once daily (QD) or twice daily (BID), depending on the assigned cohort dose level, in 21-day cycles. In a 21-day cycle, bortezomib was also administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was followed 1-2 hours later by the dose of bortezomib. In the dose-escalation phase (Part 1), participants were enrolled sequentially in groups of 3 and individually assessed for safety and dose-limiting toxicity.	Dasatinib, 100 mg QD n=3 Participants Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD n=4 Participants Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade AEs	7 Participants	3 Participants	4 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade AEs leading to discontinuation	5 Participants	1 Participants	2 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade Death	3 Participants	2 Participants	2 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade SAEs	6 Participants	2 Participants	1 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade Drug-related SAEs	2 Participants	0 Participants	0 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade Drug-related AEs leading to discontinuation	3 Participants	0 Participants	1 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade AEs, Grades 3 and 4	3 Participants	3 Participants	4 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade Drug-related AEs	6 Participants	2 Participants	4 Participants
Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs) Leading to Discontinuation, AEs Leading to Discontinuation, AEs, and Drug-related AEs by Grade Drug-related AEs, Grades 3 and 4	4 Participants	2 Participants	4 Participants

Adverse Events

Dasatinib, 100 mg QD

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Dasatinib, 140 mg QD

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Dasatinib, 50 mg BID

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dasatinib, 100 mg QD n=3 participants at risk Dasatinib, 100 mg, given QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 140 mg QD n=4 participants at risk Dasatinib, 140 mg, administered QD with 1.3 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg QD, was administered the day of and 1 day after each bortezomib dosing.In a 21-day cycle, bortezomib was administered by IV bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, QD in the morning. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.	Dasatinib, 50 mg BID n=7 participants at risk Dasatinib, 50 mg administered twice daily (BID), with 1.0 mg/m\^2 of bortezomib in 21-day cycles. Dexamethasone, fixed at 20 mg once daily (QD), was administered the day of and 1 day after each bortezomib dosing. In a 21-day cycle, bortezomib was administered by intravenous (IV) bolus twice weekly, on Days 1, 4, 8, and 11, followed by a 10-day (Days 12 to 21) rest period. In a 21-day cycle, dasatinib was taken orally every day, BID. In a 21-day cycle, dexamethasone was taken orally on Days 1, 2, 4, 5, 8, 9, 11, and 12, at the same time as dasatinib. On the days when bortezomib and dasatinib were administered together, the morning dose of dasatinib was to be followed 1-2 hours by the dose of bortezomib.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	25.0% 1/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	25.0% 1/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
General disorders Pyrexia	33.3% 1/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Infections and infestations Pneumocystis jiroveci pneumonia	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	14.3% 1/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Infections and infestations Respiratory tract infection	33.3% 1/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	14.3% 1/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	42.9% 3/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Psychiatric disorders Confusional state	33.3% 1/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Renal and urinary disorders Renal failure	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	14.3% 1/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	28.6% 2/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/3 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	0.00% 0/4 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)	14.3% 1/7 • Continuously from Day 1 until last day of study medication + 30 days (maximum reached: 10 months)

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