Trial Outcomes & Findings for Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML) (NCT NCT01218477)
NCT ID: NCT01218477
Last Updated: 2016-06-17
Results Overview
The following drug-related adverse events (AEs) occurring in the first 28 days of treatment were considered dose-limiting toxicities (DLT): Grade 4 hematologic AE lasting \>7 days; ≥Grade 3 nonhematologic AE, despite medical intervention; ≥Grade 2 AE uncontrolled by medical intervention and requiring treatment interruption for \>7 days. RP2D was that dose at which ≤1 of 6 patients had a DLT in the first 4 weeks of treatment. If \<3 patients were DLT-evaluable, up to 6 additional patients entered the same dose level. Accrual to a dose level closed if 6 patients were enrolled and \<3 were DLT-evaluable. If ≥3 patients at a dose level had no DLTs when a new patient enrolled, the dose was escalated to next level. If 1 DLT was observed in \<6 patients, ≥6 patients were required; if no additional DLT was observed, the dose was escalated to the next highest level. If ≥2 DLTs were observed in \<6 patients, that level exceeded the RP2D, and the dose was deescalated to the next lowest level.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
33 participants
Primary outcome timeframe
Day 1 to Week 80, with observation for DLT in Weeks 5-8
Results posted on
2016-06-17
Participant Flow
33 participants were enrolled; 27 were treated.
Participant milestones
| Measure |
Dasatinib, 100/140 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Participants received BMS-833923, 100 mg twice daily (BID), for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then 200 mg once daily (QD) plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
8
|
14
|
2
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
3
|
8
|
14
|
2
|
Reasons for withdrawal
| Measure |
Dasatinib, 100/140 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Participants received BMS-833923, 100 mg twice daily (BID), for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then 200 mg once daily (QD) plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Overall Study
Disease progression
|
2
|
3
|
6
|
2
|
|
Overall Study
Study drug toxicity
|
0
|
2
|
5
|
0
|
|
Overall Study
No longer meets study criteria
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
|
Overall Study
Prepared for cell transplantation
|
0
|
1
|
1
|
0
|
|
Overall Study
Administrative reason by sponsor
|
0
|
0
|
1
|
0
|
|
Overall Study
Maximum clinical benefit
|
0
|
2
|
0
|
0
|
Baseline Characteristics
Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)
Baseline characteristics by cohort
| Measure |
Dasatinib, 100/140 mg QD
n=3 Participants
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
n=8 Participants
Participants received dasatinib, 100/140 mg once daily (QD), plus BMS-833923, 50 mg, QD), depending on cohort cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
n=14 Participants
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
n=2 Participants
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then once daily (QD) plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
43.0 Years
n=5 Participants
|
57.5 Years
n=7 Participants
|
55.5 Years
n=5 Participants
|
64.5 Years
n=4 Participants
|
56.0 Years
n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
White
|
1 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
0
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
1
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
2
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Current leukemia diagnosis
Accelerated phase Ph+ CML
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Current leukemia diagnosis
Chronic phase Ph+ CML
|
1 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Current leukemia diagnosis
Myeloid blast
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Current leukemia diagnosis
Ph+ ALL
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
Current disease phase
CML-advanced phase
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Current disease phase
CML-chronic phase
|
1 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
19 Participants
n=21 Participants
|
|
Previous medication for chronic myeloid leukemia
Dasatinib
|
0 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
11 Participants
n=21 Participants
|
|
Previous medication for chronic myeloid leukemia
Imatinib
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Previous medication for chronic myeloid leukemia
Nilotinib
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Primary reason for eligibility
Cytogenetic progression
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Primary reason for eligibility
Hematologic progression
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
|
Primary reason for eligibility
Suboptimal response
|
1 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 to Week 80, with observation for DLT in Weeks 5-8Population: Participants who were dose-limiting toxicity (DLT)-evaluable (DLT-evaluable=received combination therapy on \>21 of 28 days in Weeks 5 through 8 or interrupted treatment for drug-related AEs)
The following drug-related adverse events (AEs) occurring in the first 28 days of treatment were considered dose-limiting toxicities (DLT): Grade 4 hematologic AE lasting \>7 days; ≥Grade 3 nonhematologic AE, despite medical intervention; ≥Grade 2 AE uncontrolled by medical intervention and requiring treatment interruption for \>7 days. RP2D was that dose at which ≤1 of 6 patients had a DLT in the first 4 weeks of treatment. If \<3 patients were DLT-evaluable, up to 6 additional patients entered the same dose level. Accrual to a dose level closed if 6 patients were enrolled and \<3 were DLT-evaluable. If ≥3 patients at a dose level had no DLTs when a new patient enrolled, the dose was escalated to next level. If 1 DLT was observed in \<6 patients, ≥6 patients were required; if no additional DLT was observed, the dose was escalated to the next highest level. If ≥2 DLTs were observed in \<6 patients, that level exceeded the RP2D, and the dose was deescalated to the next lowest level.
Outcome measures
| Measure |
Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD
n=24 Participants
Participants received BMS-833923 + dasatinib at 1 of 4 dosing levels: Dasatinib, 100 mg/140 mg QD, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase); BMS-833923, 50 mg once daily (QD) + dasatinib, 100 mg/140 mg QD; BMS-833923, 100 mg twice daily (BID) for 7 days, then 100 mg QD + dasatinib 100 mg/140 mg QD; or BMS-833923, 200 mg BID for 7 days, then 200 mg QD + dasatinib 100 mg/140 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days, then once daily (QD), plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase
|
50 mg
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 80Population: All patients without CCyR at dosing start date who received at least 4 weeks of dasatinib and had at least 1 on-treatment cytogenetic evaluation of the bone marrow data after at least 4 weeks on treatment
Cytogenetic response (CyR) was based on the proportion of Philadelphia chromosome-positive (Ph+) cells in metaphase analysis of bone marrow. Complete cytogenetic response (CCyR)=0 Ph+ cells; Partial CyR (PCyR)=1 to 35 Ph+ cells; Minor CyCR= 36-65 Ph+ cells; Minimal CyCR= 66-95 Ph+ cells; No response= \>96 Ph+ cells. MCyR=CCyR + PCyR. Nilo=nilotinib; SOR=suboptimal response.
Outcome measures
| Measure |
Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD
n=19 Participants
Participants received BMS-833923 + dasatinib at 1 of 4 dosing levels: Dasatinib, 100 mg/140 mg QD, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase); BMS-833923, 50 mg once daily (QD) + dasatinib, 100 mg/140 mg QD; BMS-833923, 100 mg twice daily (BID) for 7 days, then 100 mg QD + dasatinib 100 mg/140 mg QD; or BMS-833923, 200 mg BID for 7 days, then 200 mg QD + dasatinib 100 mg/140 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days, then once daily (QD), plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Percentage of Participants With a Major Cytogenetic Response (MCyR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-CP with imatinib or nilo resistance/SOR (n=6)
|
66.7 Percentage of participants
Interval 22.28 to 95.67
|
—
|
—
|
—
|
|
Percentage of Participants With a Major Cytogenetic Response (MCyR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-CP with dasatinib resistance/SOR (n=10)
|
20 Percentage of participants
Interval 2.52 to 55.61
|
—
|
—
|
—
|
|
Percentage of Participants With a Major Cytogenetic Response (MCyR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-Adv with imatinib or nilo resistance/SOR (n=3)
|
66.7 Percentage of participants
Interval 9.43 to 99.16
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 80Population: Patients without complete hematologic response at dosing start date who received at least 4 weeks of dasatinib and who had at least 1 on-treatment evaluation of both peripheral blood counts and bone marrow cytogenetic response after at least 4 weeks on treatment.
MHR was defined as complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR for CML-Adv criteria: white blood cell count (WBC) ≤upper limit normal; absolute neutrophil count (ANC) ≥1,000/mm\^3; platelets ≥100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); basophils \<5% in PB; myelocytes + metamyelocytes \< 5% in PB; no extramedullary involvement; blasts must be \<5%, if bone marrow assessment (BMA) performed. NEL had same criteria, but with lower thresholds for reconstitution of PB counts, as follows: Platelets ≥ 20,000/mm\^3 or ANC \>500/mm\^3. Confirmed MHR obtained if these criteria met and maintained for ≥28 days. CHR for CML-CP criteria WBC ≤10,000/mm\^3; platelets \<450,000/mm\^3; basophils \<5% in PB; no blasts or promyelocytes in PB; myelocytes + metamyelocytes \<5% in PB; no extramedullary involvement; blasts must be \<5% if BMA performed. Confirmed CHR obtained if these criteria met and maintained for ≥28 days. Nilo=nilotinib; SOR=suboptimal response.
Outcome measures
| Measure |
Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD
n=8 Participants
Participants received BMS-833923 + dasatinib at 1 of 4 dosing levels: Dasatinib, 100 mg/140 mg QD, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase); BMS-833923, 50 mg once daily (QD) + dasatinib, 100 mg/140 mg QD; BMS-833923, 100 mg twice daily (BID) for 7 days, then 100 mg QD + dasatinib 100 mg/140 mg QD; or BMS-833923, 200 mg BID for 7 days, then 200 mg QD + dasatinib 100 mg/140 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days, then once daily (QD), plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Percentage of Participants With a Major Hematologic Response (MHR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-CP with imatinib or nilo resistance/SOR (n=2)
|
50 Percentage of participants
Interval 1.26 to 98.74
|
—
|
—
|
—
|
|
Percentage of Participants With a Major Hematologic Response (MHR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-CP with dasatinib resistance/SOR (n=5)
|
60 Percentage of participants
Interval 14.66 to 94.73
|
—
|
—
|
—
|
|
Percentage of Participants With a Major Hematologic Response (MHR) in Chronic Myeloid Leukemia-Advanced Phase (CML-Adv) and Chronic Myeloid Leukemia-Chronic Phase (CML-CP)
CML-CP with imatinib or nilo resistance/SOR (n=1)
|
100 Percentage of participants
Interval 2.5 to 100.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 to Week 80, continuously, with observation for dose-limiting toxicities (DLTs) in Weeks 5-8Population: All participants who received at least 1 dose of study drug
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment and may or may not be related to treatment. SAE=an untoward medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug. The following drug-related AEs occurring during the first 28 days of treatment with both agents were considered to be dose-limiting toxicities (DLTs): Grade 4 hematologic AE lasting \>7 days; ≥Grade 3 nonhematologic AE, despite adequate medical intervention; ≥Grade 2 AE not controlled by medical intervention and requiring treatment interruption for \>7 days.
Outcome measures
| Measure |
Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD
n=3 Participants
Participants received BMS-833923 + dasatinib at 1 of 4 dosing levels: Dasatinib, 100 mg/140 mg QD, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase); BMS-833923, 50 mg once daily (QD) + dasatinib, 100 mg/140 mg QD; BMS-833923, 100 mg twice daily (BID) for 7 days, then 100 mg QD + dasatinib 100 mg/140 mg QD; or BMS-833923, 200 mg BID for 7 days, then 200 mg QD + dasatinib 100 mg/140 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
n=8 Participants
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
n=14 Participants
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
n=2 Participants
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days, then once daily (QD), plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
AEs leading to discontinuation
|
1 Participants
|
2 Participants
|
5 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
Drug-related AEs leading to discontinuation
|
0 Participants
|
2 Participants
|
5 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
At least 1 drug-related AE
|
0 Participants
|
8 Participants
|
13 Participants
|
2 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
Drug-related SAEs
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
DLTs
|
NA Participants
DLTs were only defined for treatment with both dasatinib and BMS-833923
|
0 Participants
|
2 Participants
|
1 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
Death
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs) Leading to Discontinuation, Drug-related AEs Leading to Discontinuation, at Least 1 Drug-related AE, and Dose-limiting Toxicities
SAEs
|
1 Participants
|
3 Participants
|
5 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 1 to Week 80Population: All participants who received at least 1 dose of study drug.
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria of the National Cancer Institute from 1 (least severe) to 4 (life threatening). ANC (\*10\^9): Grade 3, \<1.0- 0.5; Grade 4, \<0.5. Hemoglobin (mmol/L): Grade 3, \<4.9-4.0; Grade 4, \<4.0. Platelet count (\*10\^9/L): Grade 3, \<50.0-25.0; Grade 4, \<25. WBCs (\*10\^9): Grade 3, \<2.0-1.0; Grade 4, \<1.0. Hypocalcemia (mmol/L): Grade 3, \<1.75-1.5; Grade 4, \<1.5. Hyperkalemia (mmol/L): Grade 3, \>6.0-7.0; Grade 4, \>7.0. Hypokalemia (mmol/L): Grade 3, \<3.0-2.5; Grade 4, \<2.5. Hyponatremia (mmol/L), Grade 3, \<130-120; Grade 4, \<120. Hypermagnesemia (mg/dL): Grade 3, \>1.23-3.30; Grade 4, \>3.30. Phosphorus (mmol/L): Grade 3, \<0.6-0.3; Grade 4, \<0.3. Lipase (\*ULN): Grade 3, \>2.0-5.0; Grade 4, \>5.0.
Outcome measures
| Measure |
Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD
n=3 Participants
Participants received BMS-833923 + dasatinib at 1 of 4 dosing levels: Dasatinib, 100 mg/140 mg QD, depending on cohort (100 mg for those with chronic myeloid leukemia \[CML\]-chronic phase; 140 mg for those with CML-advanced phase); BMS-833923, 50 mg once daily (QD) + dasatinib, 100 mg/140 mg QD; BMS-833923, 100 mg twice daily (BID) for 7 days, then 100 mg QD + dasatinib 100 mg/140 mg QD; or BMS-833923, 200 mg BID for 7 days, then 200 mg QD + dasatinib 100 mg/140 mg QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD
n=8 Participants
Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD
|
Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
n=14 Participants
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatinib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
n=2 Participants
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days, then once daily (QD), plus dasatinib, 100 /140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Absolute neutrophil count (ANC)
|
0 Participants
|
0 Participants
|
5 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hemoglobin
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
White blood cell count (WBC)
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hypokalemia
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Platelet count (n=1, 8, 14, 2)
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hypocalcemia
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hyperkalemia
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hyponatremia
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Hypermagnesemia
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Phosphorus, inorganic (n=3, 8, 12, 2)
|
0 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
|
Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results
Lipase, total (n=3, 3,14, 2)
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Dasatinib, 100/140 mg QD
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD
Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths
Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
Serious events: 5 serious events
Other events: 14 other events
Deaths: 0 deaths
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dasatinib, 100/140 mg QD
n=3 participants at risk
Participants received dasatinib, 100/140 mg once daily (QD) (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD
n=8 participants at risk
Participants received dasatanib, 100/140 mg once daily (QD), as oral tablets plus BMS-833923, 50 mg, QD (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
n=14 participants at risk
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatanib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
n=2 participants at risk
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then 200 mg once daily (QD) plus dasatinib, 100 /140 mg QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Gastritis haemorrhagic
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3
|
12.5%
1/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3
|
25.0%
2/8
|
7.1%
1/14
|
0.00%
0/2
|
|
General disorders
Mucosal inflammation
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
General disorders
Pyrexia
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
|
33.3%
1/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine carcinoma in situ
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
General disorders
Asthenia
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Leukocytosis
|
33.3%
1/3
|
0.00%
0/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Melaena
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
Other adverse events
| Measure |
Dasatinib, 100/140 mg QD
n=3 participants at risk
Participants received dasatinib, 100/140 mg once daily (QD) (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD
n=8 participants at risk
Participants received dasatanib, 100/140 mg once daily (QD), as oral tablets plus BMS-833923, 50 mg, QD (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD
n=14 participants at risk
Participants received BMS-833923, 100 mg twice daily (BID) for 7 days then once daily (QD) + dasatanib, 100/140 mg QD, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD
n=2 participants at risk
Participants received BMS-833923, 200 mg twice daily (BID) for 7 days then 200 mg once daily (QD) plus dasatinib, 100 /140 mg QD), depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3
|
25.0%
2/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Investigations
Amylase
|
0.00%
0/3
|
25.0%
2/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Investigations
Amylase increased
|
0.00%
0/3
|
25.0%
2/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3
|
0.00%
0/8
|
21.4%
3/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3
|
12.5%
1/8
|
28.6%
4/14
|
0.00%
0/2
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3
|
62.5%
5/8
|
71.4%
10/14
|
50.0%
1/2
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Investigations
Lipase increased
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Investigations
Weight decreased
|
0.00%
0/3
|
37.5%
3/8
|
50.0%
7/14
|
0.00%
0/2
|
|
Nervous system disorders
Ageusia
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3
|
25.0%
2/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Investigations
Blood creatinine
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/3
|
25.0%
2/8
|
35.7%
5/14
|
50.0%
1/2
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
50.0%
1/2
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3
|
0.00%
0/8
|
21.4%
3/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
50.0%
1/2
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3
|
37.5%
3/8
|
50.0%
7/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Influenza
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
General disorders
Influenza like illness
|
0.00%
0/3
|
12.5%
1/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Investigations
Lipase
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
General disorders
Pyrexia
|
0.00%
0/3
|
12.5%
1/8
|
28.6%
4/14
|
0.00%
0/2
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
50.0%
4/8
|
28.6%
4/14
|
50.0%
1/2
|
|
Investigations
Blood cholesterol increased
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Herpes dermatitis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3
|
25.0%
2/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Salivary hypersecretion
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/3
|
25.0%
2/8
|
21.4%
3/14
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Vascular disorders
Hypertension
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/3
|
25.0%
2/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3
|
0.00%
0/8
|
28.6%
4/14
|
0.00%
0/2
|
|
General disorders
Oedema peripheral
|
0.00%
0/3
|
25.0%
2/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Infections and infestations
Tooth infection
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Nervous system disorders
Tremor
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3
|
0.00%
0/8
|
21.4%
3/14
|
0.00%
0/2
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3
|
12.5%
1/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
General disorders
General physical health deterioration
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
37.5%
3/8
|
57.1%
8/14
|
50.0%
1/2
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Nervous system disorders
Parosmia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/3
|
12.5%
1/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3
|
0.00%
0/8
|
28.6%
4/14
|
0.00%
0/2
|
|
General disorders
Asthenia
|
0.00%
0/3
|
12.5%
1/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Investigations
Blood cholesterol
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Investigations
Blood potassium decreased
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
General disorders
Chills
|
0.00%
0/3
|
25.0%
2/8
|
0.00%
0/14
|
50.0%
1/2
|
|
Infections and infestations
Clostridium difficile infection
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Nervous system disorders
Headache
|
0.00%
0/3
|
12.5%
1/8
|
21.4%
3/14
|
50.0%
1/2
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Reproductive system and breast disorders
Menstruation irregular
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Rhinitis
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
50.0%
4/8
|
78.6%
11/14
|
50.0%
1/2
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
37.5%
3/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Investigations
Blood lactate dehydrogenase increased
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Bronchitis
|
0.00%
0/3
|
0.00%
0/8
|
21.4%
3/14
|
0.00%
0/2
|
|
Investigations
C-reactive protein increased
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3
|
25.0%
2/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
50.0%
1/2
|
|
General disorders
Fatigue
|
0.00%
0/3
|
37.5%
3/8
|
28.6%
4/14
|
50.0%
1/2
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3
|
0.00%
0/8
|
14.3%
2/14
|
0.00%
0/2
|
|
Gastrointestinal disorders
Loose tooth
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Infections and infestations
Sinusitis
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Injury, poisoning and procedural complications
Skin wound
|
0.00%
0/3
|
12.5%
1/8
|
0.00%
0/14
|
0.00%
0/2
|
|
Nervous system disorders
Somnolence
|
0.00%
0/3
|
12.5%
1/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/3
|
0.00%
0/8
|
7.1%
1/14
|
0.00%
0/2
|
|
Investigations
White blood cell count increased
|
0.00%
0/3
|
0.00%
0/8
|
0.00%
0/14
|
50.0%
1/2
|
Additional Information
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