Dasatinib Combination Therapy With the Smoothened (SMO) Inhibitor BMS-833923 in Chronic Myeloid Leukemia (CML)
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT01218477
Collaborator
(none)
33
12
4
27
2.8
0.1
Study Details
Study Description
Brief Summary
The purpose of the study is to determine the safety and tolerability of the combination of BMS-833923 plus dasatinib in patients with chronic myeloid leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
33 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Dasatinib (BMS-354825) Combined With SMO Inhibitor (BMS-833923; XL139) in CML With Resistance or Suboptimal Response to a Prior TKI
Study Start Date
:
Jan 1, 2011
Actual Primary Completion Date
:
Apr 1, 2013
Actual Study Completion Date
:
Apr 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dasatinib, 100/140 mg QD Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase) |
Drug: Dasatinib
Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase)
Other Names:
|
| Experimental: 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 |
Drug: Dasatinib
Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase)
Other Names:
Drug: BMS-833923
Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
| Experimental: 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) |
Drug: Dasatinib
Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase)
Other Names:
Drug: BMS-833923
Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
| Experimental: 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) |
Drug: Dasatinib
Oral tablets, 100-140 mg once daily, depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase)
Other Names:
Drug: BMS-833923
Oral capsules, 50-200 mg, depending on cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase)
|
Outcome Measures
Primary Outcome Measures
- Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase [Day 1 to Week 80, with observation for DLT in Weeks 5-8]
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.
Secondary Outcome Measures
- 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) [Day 1 to Week 80]
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.
- 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) [Day 1 to Week 80]
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.
- 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 [Day 1 to Week 80, continuously, with observation for dose-limiting toxicities (DLTs) in Weeks 5-8]
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.
- Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results [Day 1 to Week 80]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria
-
Age ≥18 years
-
Diagnosis of chronic myeloid leukemia (CML) and cytogenetic positive for the Philadelphia chromosome (Ph+), documented Ph+ cells on bone marrow assessment (BMA) ≤6 weeks prior to treatment
-
Either chronic-phase CML, with <15% blasts in peripheral blood and bone marrow, or advanced-phase CML, including Ph+ acute lymphoblastic leukemia (ALL) (> 5% blasts) or hematologic progression with ≥15% blasts not in complete cytogenetic remission
-
Resistance or suboptimal response to imatinib, dasatinib, or nilotinib and no known T315I/A Abl-kinase mutation.
Key Exclusion Criteria
-
Known Abl-kinase T315I or T315A mutation
-
CCyR at baseline
-
Any serious or uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
-
Uncontrolled or significant cardiovascular disease
-
Grade 3 or higher peripheral blood counts
-
Serum calcium or phosphate below the lower limit of normal
-
Baseline hypomagnesemia and amylase or lipase at least Grade 1 or higher
-
Reduced renal function, defined as serum creatinine level >3*upper limit of normal
-
Prior therapies for CML or Ph+ ALL permitted, with the following restriction:
-
Therapy permitted with corticosteroids, hydroxyurea, or anagrelide prior to starting treatment and during the first 4 weeks on study
-
6 months or longer after stem cell transplantation
-
28 days or longer after any investigational agent
-
7 days or longer after any standard chemotherapy agent
-
Concomitant use of medications with a known risk of causing Torsades de Pointes
-
Concomitant use of strong inhibitors of the CYP3A4 isoenzyme
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of California Medical Center | San Francisco | California | United States | 94143 |
| 2 | Sidney Kimmel Cancer Center At Johns Hopkins | Baltimore | Maryland | United States | 21287 |
| 3 | Ut M.D. Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 4 | Local Institution | Hamilton | Ontario | Canada | L8N 3Z5 |
| 5 | Local Institution | Toronto | Ontario | Canada | M5G 2M9 |
| 6 | Local Institution | Helsinki | Finland | 00290 | |
| 7 | Local Institution | Bordeaux | France | 33076 | |
| 8 | Local Institution | Poitiers Cedex | France | 86021 | |
| 9 | Local Institution | Frankfurt/main | Germany | 60590 | |
| 10 | Local Institution | Bologna | Italy | 40138 | |
| 11 | Local Institution | Orbassano(To) | Italy | 10043 | |
| 12 | Local Institution | Glasgow | United Kingdom | G12 0YN |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01218477
Other Study ID Numbers:
- CA180-323
- 2010-019480-11
First Posted:
Oct 11, 2010
Last Update Posted:
Jun 17, 2016
Last Verified:
May 1, 2016
Keywords provided by Bristol-Myers Squibb
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 33 participants were enrolled; 27 were treated. |
| Arm/Group Title | Dasatinib, 100/140 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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 | 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) | 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) |
| Period Title: Overall Study | ||||
| STARTED | 3 | 8 | 14 | 2 |
| COMPLETED | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 8 | 14 | 2 |
Baseline Characteristics
| Arm/Group Title | Dasatinib, 100/140 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD | Total |
|---|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) | 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 of all reporting groups |
| Overall Participants | 3 | 8 | 14 | 2 | 27 |
| Age (Years) [Median (Full Range) ] | |||||
| Median (Full Range) [Years] |
43.0
|
57.5
|
55.5
|
64.5
|
56.0
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
1
33.3%
|
6
75%
|
7
50%
|
1
50%
|
15
55.6%
|
| Male |
2
66.7%
|
2
25%
|
7
50%
|
1
50%
|
12
44.4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||||
| White |
1
33.3%
|
7
87.5%
|
11
78.6%
|
2
100%
|
21
77.8%
|
| Black/African American |
1
33.3%
|
1
12.5%
|
2
14.3%
|
0
0%
|
4
14.8%
|
| Other |
1
33.3%
|
0
0%
|
1
7.1%
|
0
0%
|
2
7.4%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Number) [Number] | |||||
| 0 |
2
66.7%
|
2
25%
|
11
78.6%
|
1
50%
|
16
59.3%
|
| 1 |
0
0%
|
6
75%
|
3
21.4%
|
1
50%
|
10
37%
|
| 2 |
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Current leukemia diagnosis (Number) [Number] | |||||
| Accelerated phase Ph+ CML |
1
33.3%
|
0
0%
|
2
14.3%
|
0
0%
|
3
11.1%
|
| Chronic phase Ph+ CML |
1
33.3%
|
8
100%
|
8
57.1%
|
2
100%
|
19
70.4%
|
| Myeloid blast |
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
1
3.7%
|
| Ph+ ALL |
0
0%
|
0
0%
|
4
28.6%
|
0
0%
|
4
14.8%
|
| Current disease phase (Number) [Number] | |||||
| CML-advanced phase |
2
66.7%
|
0
0%
|
6
42.9%
|
0
0%
|
8
29.6%
|
| CML-chronic phase |
1
33.3%
|
8
100%
|
8
57.1%
|
2
100%
|
19
70.4%
|
| Previous medication for chronic myeloid leukemia (Number) [Number] | |||||
| Dasatinib |
0
0%
|
6
75%
|
4
28.6%
|
1
50%
|
11
40.7%
|
| Imatinib |
1
33.3%
|
1
12.5%
|
5
35.7%
|
0
0%
|
7
25.9%
|
| Nilotinib |
2
66.7%
|
1
12.5%
|
5
35.7%
|
1
50%
|
9
33.3%
|
| Primary reason for eligibility (Number) [Number] | |||||
| Cytogenetic progression |
1
33.3%
|
1
12.5%
|
4
28.6%
|
0
0%
|
6
22.2%
|
| Hematologic progression |
1
33.3%
|
1
12.5%
|
4
28.6%
|
1
50%
|
7
25.9%
|
| Suboptimal response |
1
33.3%
|
6
75%
|
6
42.9%
|
1
50%
|
14
51.9%
|
Outcome Measures
| Title | Recommended Phase 2 Dose (RP2D) of BMS-833923 Plus Dasatinib in Chronic Myeloid Leukemia-Chronic Phase |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 80, with observation for DLT in Weeks 5-8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
| Arm/Group Title | Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 24 |
| Number [mg] |
50
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 80 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 19 |
| CML-CP with imatinib or nilo resistance/SOR (n=6) |
66.7
2223.3%
|
| CML-CP with dasatinib resistance/SOR (n=10) |
20
666.7%
|
| CML-Adv with imatinib or nilo resistance/SOR (n=3) |
66.7
2223.3%
|
| Title | 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) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 80 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Dasatinib, 100/140 mg QD, Plus BMS-833923, 50-200 BID/QD |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 8 |
| CML-CP with imatinib or nilo resistance/SOR (n=2) |
50
1666.7%
|
| CML-CP with dasatinib resistance/SOR (n=5) |
60
2000%
|
| CML-CP with imatinib or nilo resistance/SOR (n=1) |
100
3333.3%
|
| Title | 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 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 80, continuously, with observation for dose-limiting toxicities (DLTs) in Weeks 5-8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug |
| Arm/Group Title | Dasatinib, 100/140 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD |
|---|---|---|---|---|
| Arm/Group Description | Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort (100 mg for those with chronic myeloid leukemia [CML]-chronic phase; 140 mg for those with CML-advanced phase) | 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 | 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) | 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) |
| Measure Participants | 3 | 8 | 14 | 2 |
| Death |
1
33.3%
|
0
0%
|
2
14.3%
|
0
0%
|
| SAEs |
1
33.3%
|
3
37.5%
|
5
35.7%
|
0
0%
|
| Drug-related SAEs |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
| AEs leading to discontinuation |
1
33.3%
|
2
25%
|
5
35.7%
|
0
0%
|
| Drug-related AEs leading to discontinuation |
0
0%
|
2
25%
|
5
35.7%
|
0
0%
|
| At least 1 drug-related AE |
0
0%
|
8
100%
|
13
92.9%
|
2
100%
|
| DLTs |
NA
NaN
|
0
0%
|
2
14.3%
|
1
50%
|
| Title | Number of Participants With Grade 3-4 Abnormalities on Laboratory Test Results |
|---|---|
| Description | 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. |
| Time Frame | Day 1 to Week 80 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study drug. |
| Arm/Group Title | Dasatinib, 100/140 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatinib, 100/140 mg QD + BMS-833923, 100 mg BID | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD |
|---|---|---|---|---|
| Arm/Group Description | 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) | Participants received dasatinib, 100/140 mg once daily (QD), depending on cohort cohort (100 mg for those with CML-chronic phase; 140 mg for those with CML-advanced phase) plus BMS-833923, 50 mg, QD | Participants received BMS-833923, 100 mg twice daily (BID), for 7 days, followed by dasatinib, 100/140 mg once daily (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) |
| Measure Participants | 3 | 8 | 14 | 2 |
| Absolute neutrophil count (ANC) |
0
0%
|
0
0%
|
5
35.7%
|
0
0%
|
| Hemoglobin |
0
0%
|
0
0%
|
3
21.4%
|
0
0%
|
| Platelet count (n=1, 8, 14, 2) |
1
33.3%
|
0
0%
|
3
21.4%
|
0
0%
|
| White blood cell count (WBC) |
0
0%
|
0
0%
|
3
21.4%
|
0
0%
|
| Hypocalcemia |
0
0%
|
0
0%
|
1
7.1%
|
0
0%
|
| Hyperkalemia |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
| Hypokalemia |
0
0%
|
0
0%
|
2
14.3%
|
0
0%
|
| Hyponatremia |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
| Hypermagnesemia |
0
0%
|
0
0%
|
1
7.1%
|
0
0%
|
| Phosphorus, inorganic (n=3, 8, 12, 2) |
0
0%
|
0
0%
|
3
21.4%
|
0
0%
|
| Lipase, total (n=3, 3,14, 2) |
0
0%
|
2
25%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | ||||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Dasatinib, 100/140 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD | ||||
| Arm/Group Description | 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) | 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) | 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) | 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) | ||||
All Cause Mortality |
||||||||
| Dasatinib, 100/140 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Dasatinib, 100/140 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 3/8 (37.5%) | 5/14 (35.7%) | 0/2 (0%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Febrile neutropenia | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Leukocytosis | 1/3 (33.3%) | 0/8 (0%) | 0/14 (0%) | 0/2 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Gastritis haemorrhagic | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Diarrhoea | 0/3 (0%) | 2/8 (25%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Vomiting | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Nausea | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Melaena | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| General disorders | ||||||||
| Mucosal inflammation | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Pyrexia | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Asthenia | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Cholecystitis | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 0/3 (0%) | 1/8 (12.5%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Clostridium difficile colitis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Clostridium difficile infection | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperkalaemia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Acute lymphocytic leukaemia | 1/3 (33.3%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Uterine carcinoma in situ | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Renal failure acute | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Dasatinib, 100/140 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 50 mg QD | Dasatanib, 100/140 mg QD + BMS-833923, 100 mg BID/QD | Dasatinib, 100 /140 mg QD+ BMS-833923, 200 mg BID/QD | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 8/8 (100%) | 14/14 (100%) | 2/2 (100%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Thrombocytopenia | 0/3 (0%) | 0/8 (0%) | 3/14 (21.4%) | 0/2 (0%) | ||||
| Leukopenia | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Neutropenia | 0/3 (0%) | 0/8 (0%) | 4/14 (28.6%) | 0/2 (0%) | ||||
| Anaemia | 0/3 (0%) | 0/8 (0%) | 4/14 (28.6%) | 0/2 (0%) | ||||
| Leukocytosis | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Cardiac disorders | ||||||||
| Pericardial effusion | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Eye disorders | ||||||||
| Lacrimation increased | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Constipation | 0/3 (0%) | 1/8 (12.5%) | 4/14 (28.6%) | 0/2 (0%) | ||||
| Anal fistula | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Diarrhoea | 0/3 (0%) | 3/8 (37.5%) | 7/14 (50%) | 0/2 (0%) | ||||
| Dry mouth | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Gingival bleeding | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Vomiting | 0/3 (0%) | 4/8 (50%) | 4/14 (28.6%) | 1/2 (50%) | ||||
| Salivary hypersecretion | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Stomatitis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Abdominal pain | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Pancreatitis | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Eructation | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Flatulence | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Nausea | 0/3 (0%) | 3/8 (37.5%) | 8/14 (57.1%) | 1/2 (50%) | ||||
| Abdominal distension | 0/3 (0%) | 1/8 (12.5%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Abdominal pain upper | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Dyspepsia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Gastritis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Gastrointestinal toxicity | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Loose tooth | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| General disorders | ||||||||
| Influenza like illness | 0/3 (0%) | 1/8 (12.5%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Pyrexia | 0/3 (0%) | 1/8 (12.5%) | 4/14 (28.6%) | 0/2 (0%) | ||||
| Oedema peripheral | 0/3 (0%) | 2/8 (25%) | 0/14 (0%) | 0/2 (0%) | ||||
| General physical health deterioration | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Asthenia | 0/3 (0%) | 1/8 (12.5%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Chills | 0/3 (0%) | 2/8 (25%) | 0/14 (0%) | 1/2 (50%) | ||||
| Fatigue | 0/3 (0%) | 3/8 (37.5%) | 4/14 (28.6%) | 1/2 (50%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Influenza | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Upper respiratory tract infection | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Herpes dermatitis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Tooth infection | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Clostridium difficile infection | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Rhinitis | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Urinary tract infection | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Bronchitis | 0/3 (0%) | 0/8 (0%) | 3/14 (21.4%) | 0/2 (0%) | ||||
| Sinusitis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Tooth abscess | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Contusion | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 1/2 (50%) | ||||
| Fall | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 1/2 (50%) | ||||
| Skin wound | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Investigations | ||||||||
| Amylase | 0/3 (0%) | 2/8 (25%) | 0/14 (0%) | 0/2 (0%) | ||||
| Amylase increased | 0/3 (0%) | 2/8 (25%) | 0/14 (0%) | 0/2 (0%) | ||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Lipase increased | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Weight decreased | 0/3 (0%) | 3/8 (37.5%) | 7/14 (50%) | 0/2 (0%) | ||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Blood creatinine | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Lipase | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Blood cholesterol increased | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Blood cholesterol | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Blood potassium decreased | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| C-reactive protein increased | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| White blood cell count increased | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypokalaemia | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Hypocalcaemia | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Hypophosphataemia | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Decreased appetite | 0/3 (0%) | 2/8 (25%) | 3/14 (21.4%) | 0/2 (0%) | ||||
| Hypomagnesaemia | 0/3 (0%) | 2/8 (25%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Hyperkalaemia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Dehydration | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/3 (0%) | 0/8 (0%) | 3/14 (21.4%) | 0/2 (0%) | ||||
| Muscle spasms | 0/3 (0%) | 2/8 (25%) | 5/14 (35.7%) | 1/2 (50%) | ||||
| Musculoskeletal chest pain | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Joint stiffness | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Musculoskeletal stiffness | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Myalgia | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Pain in extremity | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Bone pain | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Back pain | 0/3 (0%) | 3/8 (37.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Intervertebral disc protrusion | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Nervous system disorders | ||||||||
| Dysgeusia | 0/3 (0%) | 5/8 (62.5%) | 10/14 (71.4%) | 1/2 (50%) | ||||
| Ageusia | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Paraesthesia | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 1/2 (50%) | ||||
| Tremor | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Ataxia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Neuropathy peripheral | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Parosmia | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/8 (0%) | 0/14 (0%) | 1/2 (50%) | ||||
| Headache | 0/3 (0%) | 1/8 (12.5%) | 3/14 (21.4%) | 1/2 (50%) | ||||
| Dizziness | 0/3 (0%) | 2/8 (25%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Somnolence | 0/3 (0%) | 1/8 (12.5%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/3 (0%) | 2/8 (25%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Confusional state | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Sleep disorder | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Menstruation irregular | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Nasal dryness | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Oropharyngeal pain | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Pleural effusion | 0/3 (0%) | 0/8 (0%) | 2/14 (14.3%) | 0/2 (0%) | ||||
| Hiccups | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Epistaxis | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Cough | 0/3 (0%) | 0/8 (0%) | 3/14 (21.4%) | 0/2 (0%) | ||||
| Dyspnoea | 0/3 (0%) | 1/8 (12.5%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne | 0/3 (0%) | 2/8 (25%) | 0/14 (0%) | 0/2 (0%) | ||||
| Erythema nodosum | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Rash | 0/3 (0%) | 2/8 (25%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Skin mass | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Dry skin | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Alopecia | 0/3 (0%) | 4/8 (50%) | 11/14 (78.6%) | 1/2 (50%) | ||||
| Night sweats | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/3 (0%) | 1/8 (12.5%) | 0/14 (0%) | 0/2 (0%) | ||||
| Orthostatic hypotension | 0/3 (0%) | 0/8 (0%) | 1/14 (7.1%) | 0/2 (0%) | ||||
Limitations/Caveats
Bristol-Myers Squibb discontinued research in the area of smoothened inhibitors. This study was completed early and limited efficacy data was published in a synoptic clinical study report .
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01218477
Other Study ID Numbers:
- CA180-323
- 2010-019480-11
First Posted:
Oct 11, 2010
Last Update Posted:
Jun 17, 2016
Last Verified:
May 1, 2016