Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00101660
Collaborator
(none)
387
85
1
37.9
4.6
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
387 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib
Study Start Date
:
Feb 1, 2005
Actual Primary Completion Date
:
Sep 1, 2006
Actual Study Completion Date
:
Apr 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dasatinib, 70 mg twice daily (BID) Dasatanib, 70 mg twice daily (BID), with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
Drug: Dasatinib
Tablets; oral; 70 mg BID, depending on response
|
Outcome Measures
Primary Outcome Measures
- Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR) [2 years]
Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.
Secondary Outcome Measures
- Number of Imatinib-intolerant Participants With MCyR [Baseline to 2 years]
Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
- Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months [12 and 24 Months]
Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.
- Median Time From First Dosing Date to Date of MCyR [Baseline (within 4 weeks of Day 1) and every 12 weeks]
MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
- Number of Participants With Complete Hematologic Response (CHR) [Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study]
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
- Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months [12 and 24 months]
Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
- Median Time From First Dosing Until CHR [Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study]
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
- Number of Participants With Major Molecular Response (MMR) [Baseline to 2 years]
MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor.
- Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores [Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.]
Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.
- Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE [Continuously, from baseline through 2 years]
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
- Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE [Continuously, from baseline through 2 years]
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
- Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib [Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.]
Blood samples were collected for PK to be included in separate population PK analyses.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Age of 18 years and older.
-
Chronic myeloid leukemia (CML)
-
Previous treatment with imatinib at a dose of >600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
-
CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
-
Intolerance to imatinib at any dose
-
Adequate organ function
-
Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.
Exclusion Criteria:
-
Woman who are pregnant or breastfeeding
-
Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above
-
Previous diagnosis of accelerated phase or blast crisis CML.
-
Participants who are eligible and willing to undergo transplantation during the screening period
-
Uncontrolled or significant cardiovascular disease
-
Use of imatinib within 7 days.
-
Use of interferon or cytarabine within 14 days
-
Use of a targeted small-molecule anticancer agent within 14 days
-
Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
-
Prior therapy with dasatinib.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Local Institution | Anaheim | California | United States | |
| 2 | Local Institution | Loma Linda | California | United States | |
| 3 | Local Institution | Los Angeles | California | United States | |
| 4 | Local Institution | Stanford | California | United States | |
| 5 | Local Institution | Vallejo | California | United States | |
| 6 | Local Institution | Hartford | Connecticut | United States | |
| 7 | Local Institution | Washington | District of Columbia | United States | |
| 8 | Local Institution | Jacksonville | Florida | United States | |
| 9 | Local Institution | Tampa | Florida | United States | |
| 10 | Local Institution | Atlanta | Georgia | United States | |
| 11 | Local Institution | Chicago | Illinois | United States | |
| 12 | Local Institution | Indianapolis | Indiana | United States | |
| 13 | Local Institution | Kansas City | Kansas | United States | |
| 14 | Local Institution | Baltimore | Maryland | United States | |
| 15 | Local Institution | Boston | Massachusetts | United States | |
| 16 | Local Institution | Detroit | Michigan | United States | |
| 17 | Local Institution | Kansas City | Missouri | United States | |
| 18 | Local Institution | St. Louis | Missouri | United States | |
| 19 | Local Institution | Omaha | Nebraska | United States | |
| 20 | Local Institution | Hackensack | New Jersey | United States | |
| 21 | Local Institution | New Brunswick | New Jersey | United States | |
| 22 | Local Institution | New York | New York | United States | |
| 23 | Local Institution | Portland | Oregon | United States | |
| 24 | Local Institution | Philadelphia | Pennsylvania | United States | |
| 25 | Local Institution | Pittsburgh | Pennsylvania | United States | |
| 26 | Local Institution | Greenville | South Carolina | United States | |
| 27 | Local Institution | Nashville | Tennessee | United States | |
| 28 | Local Institution | Dallas | Texas | United States | |
| 29 | Local Institution | Houston | Texas | United States | |
| 30 | Local Institution | San Antonio | Texas | United States | |
| 31 | Local Institution | Tyler | Texas | United States | |
| 32 | Local Institution | Spokane | Washington | United States | |
| 33 | Local Institution | St. Leonards | New South Wales | Australia | |
| 34 | Local Institution | South Brisbane | Queensland | Australia | |
| 35 | Local Institution | Adelaide | South Australia | Australia | |
| 36 | Local Institution | East Mebourne | Victoria | Australia | |
| 37 | Local Institution | Parkville | Victoria | Australia | |
| 38 | Local Institution | Wein | Austria | ||
| 39 | Local Institution | B-Leuven | Belgium | ||
| 40 | Local Institution | Bruxelles | Belgium | ||
| 41 | Local Institution | Edegem | Belgium | ||
| 42 | Local Institution | Yvoir | Belgium | ||
| 43 | Local Institution | Vancouver | British Columbia | Canada | |
| 44 | Local Institution | Toronto | Ontario | Canada | |
| 45 | Local Institution | Montreal | Quebec | Canada | |
| 46 | Local Institution | Aarhus | Denmark | ||
| 47 | Local Institution | Helsinki | Finland | ||
| 48 | Local Institution | Lille Cedex | France | ||
| 49 | Local Institution | Lyon Cedex 03 | France | ||
| 50 | Local Institution | Nantes | France | ||
| 51 | Local Institution | Paris Cedex 10 | France | ||
| 52 | Local Institution | Pessac | France | ||
| 53 | Local Institution | Poitiers Cedex | France | ||
| 54 | Local Institution | Strasbourg Cedex | France | ||
| 55 | Local Institution | Hamburg | Germany | ||
| 56 | Local Institution | Leipzig | Germany | ||
| 57 | Local Institution | Mainz | Germany | ||
| 58 | Local Institution | Mannheim | Germany | ||
| 59 | Local Institution | Co Galway | Galway | Ireland | |
| 60 | Local Institution | Dublin | Ireland | ||
| 61 | Local Institution | Ramat-Gan | Israel | ||
| 62 | Local Institution | Bari | Italy | ||
| 63 | Local Institution | Bologna | Italy | ||
| 64 | Local Institution | Milano | Italy | ||
| 65 | Local Institution | Napoli | Italy | ||
| 66 | Local Institution | Orbassano | Italy | ||
| 67 | Local Institution | Roma | Italy | ||
| 68 | Local Institution | Kyunggi-Do | Korea, Republic of | ||
| 69 | Local Institution | Nijmegen | Netherlands | ||
| 70 | Local Institution | Rotterdam | Netherlands | ||
| 71 | Local Institution | Trondheim | Norway | ||
| 72 | Local Institution | Lima | Peru | ||
| 73 | Local Institution | Singapore | Singapore | ||
| 74 | Local Institution | Parktown | Gauteng | South Africa | |
| 75 | Local Institution | Soweto | Gauteng | South Africa | |
| 76 | Local Institution | Barcelona | Spain | ||
| 77 | Local Institution | Madrid | Spain | ||
| 78 | Local Institution | Gothenburg | Sweden | ||
| 79 | Local Institution | Lund | Sweden | ||
| 80 | Local Institution | Stockholm | Sweden | ||
| 81 | Local Institution | Umea | Sweden | ||
| 82 | Local Institution | Uppsala | Sweden | ||
| 83 | Local Instituion | Basel | Switzerland | ||
| 84 | Local Institution | Glasgow | Central | United Kingdom | |
| 85 | Local Institution | London | Greater London | United Kingdom |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Publications
- Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007 Mar 15;109(6):2303-9. Epub 2006 Nov 30. Erratum in: Blood. 2007 Sep 1;110(5):1438.
- Müller MC, Cortes JE, Kim DW, Druker BJ, Erben P, Pasquini R, Branford S, Hughes TP, Radich JP, Ploughman L, Mukhopadhyay J, Hochhaus A. Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations. Blood. 2009 Dec 3;114(24):4944-53. doi: 10.1182/blood-2009-04-214221. Epub 2009 Sep 24.
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00101660
Other Study ID Numbers:
- CA180-013
- NCT00112801
First Posted:
Jan 13, 2005
Last Update Posted:
Mar 2, 2012
Last Verified:
Feb 1, 2012
Keywords provided by Bristol-Myers Squibb
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Imatinib-intolerant | Imatinib-resistant |
|---|---|---|
| Arm/Group Description | Imatinib intolerance was defined as: Grade 3 or greater nonhematologic toxicity that is imatinib-related or Grade 4 hematologic toxicity that is imatinib-related lasting more than 7 days. | Imatinib resistance, acquired or primary. Acquired resistance: participants who achieve major cytogenetic response (MCyR) or complete hematologic response (CHR) on imatinib at any dose prior to progression, defined by 1 of the following: loss of MCyR, loss of CHR, or increasing white blood cell (WBC) count. Primary resistance: participants who never achieve MCyR or CHR at any dose, and meet 1 of the following: continuously increasing WBC count on at least 2 consecutive evaluations at least 2 weeks apart, with the final assessment showing a doubling of WBC from nadir to ≥20,000/mm^3; an absolute increase in WBC by more than 50,000/mm^3 above lowest count after starting imatinib; no CHR after 3 months; no cytogenetic response (CyR) after 6 months; or no MCyR after 12 months. Resistance was also defined as chronic myeloid leukemia (CML) with resistance to imatinib ≤600mg/d with genetic mutation in BCR-ABL gene (L248V, G250E, Q252H/R, Y253H/F, E255K/V, T315I/D, F317L, H369P/R). |
| Period Title: Overall Study | ||
| STARTED | 99 | 288 |
| COMPLETED | 99 | 288 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Imatinib-intolerant | Imatinib-resistant | Total |
|---|---|---|---|
| Arm/Group Description | Imatinib intolerance was defined as: Grade 3 or greater nonhematologic toxicity that is imatinib-related or Grade 4 hematologic toxicity that is imatinib-related lasting more than 7 days. | Imatinib resistance, acquired or primary. Acquired resistance: participants who achieve major cytogenetic response (MCyR) or complete hematologic response (CHR) on imatinib at any dose prior to progression, defined by 1 of the following: loss of MCyR, loss of CHR, or increasing white blood cell (WBC) count. Primary resistance: participants who never achieve MCyR or CHR at any dose, and meet 1 of the following: continuously increasing WBC count on at least 2 consecutive evaluations at least 2 weeks apart, with the final assessment showing a doubling of WBC from nadir to ≥20,000/mm^3; an absolute increase in WBC by more than 50,000/mm^3 above lowest count after starting imatinib; no CHR after 3 months; no cytogenetic response (CyR) after 6 months; or no MCyR after 12 months. Resistance was also defined as chronic myeloid leukemia (CML) with resistance to imatinib ≤600mg/d with genetic mutation in BCR-ABL gene (L248V, G250E, Q252H/R, Y253H/F, E255K/V, T315I/D, F317L, H369P/R). | Total of all reporting groups |
| Overall Participants | 99 | 288 | 387 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
54.6
(12.5)
|
55.7
(13.5)
|
55.4
(13.3)
|
| Age, Customized (Number) [Number] | |||
| Between 21 and 45 years |
25
25.3%
|
78
27.1%
|
103
26.6%
|
| Between 46 and 65 years |
55
55.6%
|
131
45.5%
|
186
48.1%
|
| Between 66 and 75 years |
17
17.2%
|
65
22.6%
|
82
21.2%
|
| > 75 years |
2
2%
|
14
4.9%
|
16
4.1%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
57
57.6%
|
139
48.3%
|
196
50.6%
|
| Male |
42
42.4%
|
149
51.7%
|
191
49.4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White |
93
93.9%
|
252
87.5%
|
345
89.1%
|
| Black/African American |
2
2%
|
13
4.5%
|
15
3.9%
|
| Asian |
3
3%
|
10
3.5%
|
13
3.4%
|
| Other |
1
1%
|
12
4.2%
|
13
3.4%
|
| Not reported |
0
0%
|
1
0.3%
|
1
0.3%
|
| Performance Status - Eastern Cooperative Oncology Group Scale (ECOG) Score (Number) [Number] | |||
| 0 |
71
71.7%
|
205
71.2%
|
276
71.3%
|
| 1 |
28
28.3%
|
77
26.7%
|
105
27.1%
|
| 2 |
0
0%
|
3
1%
|
3
0.8%
|
| 3 |
0
0%
|
0
0%
|
0
0%
|
| 4 |
0
0%
|
0
0%
|
0
0%
|
| 5 |
0
0%
|
0
0%
|
0
0%
|
| Not reported |
0
0%
|
3
1%
|
3
0.8%
|
| Functional Assessment of Cancer Therapy-General (FACT-G) (Units on a scale) [Mean (Standard Deviation) ] | |||
| Total FACT-G |
81.1
(14.4)
|
82.4
(13.1)
|
82.1
(13.4)
|
| PWB |
22.0
(5.1)
|
21.6
(5.2)
|
21.7
(5.2)
|
| SWB |
23.0
(4.4)
|
23.0
(4.5)
|
23.0
(4.4)
|
| EWB |
17.3
(4.0)
|
18.4
(3.7)
|
18.1
(3.8)
|
| FWB |
18.7
(5.5)
|
19.6
(5.6)
|
19.4
(5.6)
|
Outcome Measures
| Title | Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR) |
|---|---|
| Description | Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All imatinib-resistant participants who received treatment. |
| Arm/Group Title | Dasatinib, 70 mg, Twice Daily (BID) |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 288 |
| Number [Participants] |
159
160.6%
|
| Title | Number of Imatinib-intolerant Participants With MCyR |
|---|---|
| Description | Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases. |
| Time Frame | Baseline to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All imatinib-intolerant participants who received treatment. |
| Arm/Group Title | Dastinib, 70 mg, BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 99 |
| Number [Participants] |
81
81.8%
|
| Title | Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months |
|---|---|
| Description | Based on the Kaplan-Meier estimate of the duration of response. Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases. |
| Time Frame | 12 and 24 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population is limited to responders (those who acheived MCyR) who were also assessed for duration of MCyR. |
| Arm/Group Title | Dasatanib, 70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 240 |
| Imatinib-intolerant group: 12 months (n=81) |
98.5
99.5%
|
| Imatinib-intolerant group: 24 months (n=81) |
96.7
97.7%
|
| Imatinib-resistant group: 12 months (n=159) |
93.7
94.6%
|
| Imatinib-resistant group: 24 months (n=159) |
83.6
84.4%
|
| Title | Median Time From First Dosing Date to Date of MCyR |
|---|---|
| Description | MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases. |
| Time Frame | Baseline (within 4 weeks of Day 1) and every 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population is limited to responders (those who acheived MCyR) only |
| Arm/Group Title | Dasatinib, 70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 240 |
| Imatinib-intolerant |
2.79
|
| Imatinib-resistant |
2.92
|
| Title | Number of Participants With Complete Hematologic Response (CHR) |
|---|---|
| Description | CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Time Frame | Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment. |
| Arm/Group Title | Dasatinib, 70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg twice BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 387 |
| Imatinib-intolerant (n=99) |
93
93.9%
|
| Imatinib-resistant (n=288) |
259
261.6%
|
| Title | Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months |
|---|---|
| Description | Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Time Frame | 12 and 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population limited to responders (those achieving CHR) only |
| Arm/Group Title | Dasatinib,70 mg BID |
|---|---|
| Arm/Group Description | Dasatanib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 352 |
| Imatinib-intolerant: 12 months (n=93) |
97.7
98.7%
|
| Imatinib-intolerant: 24 months (n=93) |
93.5
94.4%
|
| Imatinib-resistant: 12 months (n=259) |
90.4
91.3%
|
| Imatinib-resistant: 24 months (n=259) |
78.8
79.6%
|
| Title | Median Time From First Dosing Until CHR |
|---|---|
| Description | CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets <450,000/mm^3; no blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date. |
| Time Frame | Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Population limited to responders (those achieving CHR) only |
| Arm/Group Title | Dasatinib, 70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg twice BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 352 |
| Imatinib-intolerant (n=93) |
0.49
|
| Imatinib-resistant (n=259) |
0.53
|
| Title | Number of Participants With Major Molecular Response (MMR) |
|---|---|
| Description | MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor. |
| Time Frame | Baseline to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment. |
| Arm/Group Title | Dasatinib, 70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 387 |
| Imatinib-intolerant (n=99) |
73
73.7%
|
| Imatinib-resistant (n=288) |
102
103%
|
| Title | Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores |
|---|---|
| Description | Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, & FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics. |
| Time Frame | Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants with assessments at baseline and timepoint |
| Arm/Group Title | Dasatinib,70 mg BID |
|---|---|
| Arm/Group Description | Dasatanib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 321 |
| Imatinib-intolerant: Total FACT-G (n=80) |
34
34.3%
|
| Imatinib-intolerant: PWB (n=80) |
36
36.4%
|
| Imatinib-intolerant: SWB (n=80) |
33
33.3%
|
| Imatinib-intolerant: EWB (n=80) |
40
40.4%
|
| Imatinib-intolerant: FWB (n=80) |
32
32.3%
|
| Imatinib-resistant: Total FACT-G (n=241) |
107
108.1%
|
| Imatinib-resistant: PWB (n=241) |
103
104%
|
| Imatinib-resistant: SWB (n=241) |
94
94.9%
|
| Imatinib-resistant: EWB (n=241) |
107
108.1%
|
| Imatinib-resistant: FWB (n=241) |
89
89.9%
|
| Title | Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death) |
| Time Frame | Continuously, from baseline through 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All imitanib-intolerant participants who received treatment. |
| Arm/Group Title | Dasatinib,70 mg BID |
|---|---|
| Arm/Group Description | Dasatanib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 99 |
| Drug-related AEs |
97
98%
|
| Death within 30 days of last dose |
0
0%
|
| Deaths |
0
0%
|
| On-study AEs leading to discontinuation |
16
16.2%
|
| SAEs |
48
48.5%
|
| Grade 3-4 thrombocytopenia |
32
32.3%
|
| Grade 3-4 neutropenia |
39
39.4%
|
| Any AE |
98
99%
|
| Title | Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE |
|---|---|
| Description | AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death) |
| Time Frame | Continuously, from baseline through 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All imitanib-resistant participants who received treatment. |
| Arm/Group Title | Dasatinib,70 mg BID |
|---|---|
| Arm/Group Description | Dasatinib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. a |
| Measure Participants | 288 |
| Drug-related AEs |
281
283.8%
|
| Death within 30 days of last dose |
8
8.1%
|
| Deaths |
19
19.2%
|
| On-study AEs leading to Discontinuation |
53
53.5%
|
| SAEs |
146
147.5%
|
| Grade 3-4 thrombocytopenia |
156
157.6%
|
| Grade 3-4 neutropenia |
154
155.6%
|
| Any AE |
288
290.9%
|
| Title | Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib |
|---|---|
| Description | Blood samples were collected for PK to be included in separate population PK analyses. |
| Time Frame | Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose. |
Outcome Measure Data
| Analysis Population Description |
|---|
| No study-specific PK analyses were planned for this report. |
| Arm/Group Title | Dasatinib |
|---|---|
| Arm/Group Description | Dasatanib, 70 mg BID, with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Intolerant | Resistant | ||
| Arm/Group Description | ||||
All Cause Mortality |
||||
| Intolerant | Resistant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Intolerant | Resistant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 48/99 (48.5%) | 146/288 (50.7%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 2/99 (2%) | 6/288 (2.1%) | ||
| NEUTROPENIA | 0/99 (0%) | 1/288 (0.3%) | ||
| LEUKOCYTOSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| PANCYTOPENIA | 0/99 (0%) | 2/288 (0.7%) | ||
| SPLENOMEGALY | 0/99 (0%) | 1/288 (0.3%) | ||
| THROMBOCYTOPENIA | 0/99 (0%) | 8/288 (2.8%) | ||
| FEBRILE NEUTROPENIA | 2/99 (2%) | 7/288 (2.4%) | ||
| Cardiac disorders | ||||
| CYANOSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| NODAL RHYTHM | 1/99 (1%) | 0/288 (0%) | ||
| PALPITATIONS | 0/99 (0%) | 1/288 (0.3%) | ||
| PERICARDITIS | 1/99 (1%) | 1/288 (0.3%) | ||
| CARDIOMYOPATHY | 0/99 (0%) | 1/288 (0.3%) | ||
| ANGINA PECTORIS | 2/99 (2%) | 1/288 (0.3%) | ||
| ANGINA UNSTABLE | 0/99 (0%) | 1/288 (0.3%) | ||
| CARDIAC FAILURE | 1/99 (1%) | 2/288 (0.7%) | ||
| ATRIAL FIBRILLATION | 1/99 (1%) | 7/288 (2.4%) | ||
| MYOCARDIAL ISCHAEMIA | 0/99 (0%) | 1/288 (0.3%) | ||
| PERICARDIAL EFFUSION | 1/99 (1%) | 3/288 (1%) | ||
| DIASTOLIC DYSFUNCTION | 1/99 (1%) | 1/288 (0.3%) | ||
| MYOCARDIAL INFARCTION | 1/99 (1%) | 0/288 (0%) | ||
| VENTRICULAR ARRHYTHMIA | 0/99 (0%) | 1/288 (0.3%) | ||
| ACUTE CORONARY SYNDROME | 0/99 (0%) | 1/288 (0.3%) | ||
| CORONARY ARTERY DISEASE | 0/99 (0%) | 1/288 (0.3%) | ||
| LEFT VENTRICULAR FAILURE | 1/99 (1%) | 0/288 (0%) | ||
| MITRAL VALVE INCOMPETENCE | 1/99 (1%) | 0/288 (0%) | ||
| VENTRICULAR EXTRASYSTOLES | 0/99 (0%) | 1/288 (0.3%) | ||
| CARDIAC FAILURE CONGESTIVE | 5/99 (5.1%) | 9/288 (3.1%) | ||
| ACUTE MYOCARDIAL INFARCTION | 0/99 (0%) | 2/288 (0.7%) | ||
| LEFT VENTRICULAR DYSFUNCTION | 2/99 (2%) | 1/288 (0.3%) | ||
| SUPRAVENTRICULAR TACHYCARDIA | 0/99 (0%) | 1/288 (0.3%) | ||
| Ear and labyrinth disorders | ||||
| EAR HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| Endocrine disorders | ||||
| GOITRE | 0/99 (0%) | 1/288 (0.3%) | ||
| Gastrointestinal disorders | ||||
| ILEUS | 0/99 (0%) | 1/288 (0.3%) | ||
| NAUSEA | 1/99 (1%) | 2/288 (0.7%) | ||
| COLITIS | 1/99 (1%) | 1/288 (0.3%) | ||
| MELAENA | 1/99 (1%) | 0/288 (0%) | ||
| VOMITING | 1/99 (1%) | 3/288 (1%) | ||
| DIARRHOEA | 2/99 (2%) | 10/288 (3.5%) | ||
| ENTERITIS | 1/99 (1%) | 0/288 (0%) | ||
| GASTRITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| GINGIVITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| STOMATITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| ANAL FISSURE | 0/99 (0%) | 1/288 (0.3%) | ||
| PANCREATITIS | 1/99 (1%) | 0/288 (0%) | ||
| PERIODONTITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| ABDOMINAL PAIN | 0/99 (0%) | 4/288 (1.4%) | ||
| ANAL HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| RECTAL HAEMORRHAGE | 0/99 (0%) | 2/288 (0.7%) | ||
| ABDOMINAL PAIN LOWER | 0/99 (0%) | 1/288 (0.3%) | ||
| ABDOMINAL PAIN UPPER | 1/99 (1%) | 0/288 (0%) | ||
| OESOPHAGEAL STENOSIS | 1/99 (1%) | 0/288 (0%) | ||
| INTESTINAL OBSTRUCTION | 0/99 (0%) | 1/288 (0.3%) | ||
| HAEMORRHOIDAL HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| LARGE INTESTINE PERFORATION | 0/99 (0%) | 1/288 (0.3%) | ||
| GASTROINTESTINAL HAEMORRHAGE | 0/99 (0%) | 4/288 (1.4%) | ||
| INGUINAL HERNIA, OBSTRUCTIVE | 0/99 (0%) | 1/288 (0.3%) | ||
| ABDOMINAL STRANGULATED HERNIA | 0/99 (0%) | 2/288 (0.7%) | ||
| LOWER GASTROINTESTINAL HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| General disorders | ||||
| PAIN | 0/99 (0%) | 1/288 (0.3%) | ||
| DEATH | 0/99 (0%) | 1/288 (0.3%) | ||
| FATIGUE | 0/99 (0%) | 3/288 (1%) | ||
| MALAISE | 1/99 (1%) | 1/288 (0.3%) | ||
| PYREXIA | 3/99 (3%) | 26/288 (9%) | ||
| ASTHENIA | 0/99 (0%) | 1/288 (0.3%) | ||
| CHEST PAIN | 1/99 (1%) | 2/288 (0.7%) | ||
| ADVERSE EVENT | 1/99 (1%) | 0/288 (0%) | ||
| Hepatobiliary disorders | ||||
| CHOLECYSTITIS | 1/99 (1%) | 1/288 (0.3%) | ||
| Immune system disorders | ||||
| HYPERSENSITIVITY | 1/99 (1%) | 2/288 (0.7%) | ||
| ANAPHYLACTIC REACTION | 0/99 (0%) | 1/288 (0.3%) | ||
| Infections and infestations | ||||
| INFECTION | 0/99 (0%) | 3/288 (1%) | ||
| INFLUENZA | 0/99 (0%) | 1/288 (0.3%) | ||
| PNEUMONIA | 5/99 (5.1%) | 11/288 (3.8%) | ||
| BRONCHITIS | 1/99 (1%) | 4/288 (1.4%) | ||
| CELLULITIS | 2/99 (2%) | 4/288 (1.4%) | ||
| APPENDICITIS | 1/99 (1%) | 0/288 (0%) | ||
| OSTEOMYELITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| DIVERTICULITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| PYELONEPHRITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| GASTROENTERITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| LOBAR PNEUMONIA | 0/99 (0%) | 1/288 (0.3%) | ||
| BRONCHOPNEUMONIA | 0/99 (0%) | 2/288 (0.7%) | ||
| PNEUMONIA FUNGAL | 0/99 (0%) | 1/288 (0.3%) | ||
| FEBRILE INFECTION | 1/99 (1%) | 0/288 (0%) | ||
| VIRAL PHARYNGITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| ESCHERICHIA SEPSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| PERIRECTAL ABSCESS | 0/99 (0%) | 1/288 (0.3%) | ||
| LOCALISED INFECTION | 0/99 (0%) | 1/288 (0.3%) | ||
| GASTROENTERITIS VIRAL | 0/99 (0%) | 1/288 (0.3%) | ||
| HERPES VIRUS INFECTION | 0/99 (0%) | 1/288 (0.3%) | ||
| CYTOMEGALOVIRUS COLITIS | 1/99 (1%) | 0/288 (0%) | ||
| URINARY TRACT INFECTION | 0/99 (0%) | 1/288 (0.3%) | ||
| PHARYNGOLARYNGEAL ABSCESS | 1/99 (1%) | 0/288 (0%) | ||
| RESPIRATORY TRACT INFECTION | 1/99 (1%) | 0/288 (0%) | ||
| PNEUMOCYSTIS JIROVECI PNEUMONIA | 0/99 (0%) | 2/288 (0.7%) | ||
| LOWER RESPIRATORY TRACT INFECTION | 1/99 (1%) | 0/288 (0%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 1/99 (1%) | 1/288 (0.3%) | ||
| Injury, poisoning and procedural complications | ||||
| OVERDOSE | 0/99 (0%) | 1/288 (0.3%) | ||
| SKIN LACERATION | 0/99 (0%) | 1/288 (0.3%) | ||
| JOINT DISLOCATION | 0/99 (0%) | 1/288 (0.3%) | ||
| SUBDURAL HAEMATOMA | 0/99 (0%) | 1/288 (0.3%) | ||
| ACCIDENTAL OVERDOSE | 0/99 (0%) | 1/288 (0.3%) | ||
| FACIAL BONES FRACTURE | 0/99 (0%) | 1/288 (0.3%) | ||
| PROCEDURAL COMPLICATION | 0/99 (0%) | 1/288 (0.3%) | ||
| Investigations | ||||
| LIPASE | 1/99 (1%) | 0/288 (0%) | ||
| PROLONGED | 0/99 (0%) | 0/288 (0%) | ||
| PLEUROSCOPY | 0/99 (0%) | 1/288 (0.3%) | ||
| PLATELET COUNT | 0/99 (0%) | 2/288 (0.7%) | ||
| WEIGHT DECREASED | 0/99 (0%) | 1/288 (0.3%) | ||
| HAEMOGLOBIN DECREASED | 0/99 (0%) | 2/288 (0.7%) | ||
| BLOOD CULTURE POSITIVE | 0/99 (0%) | 1/288 (0.3%) | ||
| BLOOD CREATINE INCREASED | 0/99 (0%) | 1/288 (0.3%) | ||
| PLATELET COUNT DECREASED | 1/99 (1%) | 2/288 (0.7%) | ||
| BLOOD POTASSIUM DECREASED | 0/99 (0%) | 1/288 (0.3%) | ||
| BIOPSY BONE MARROW ABNORMAL | 0/99 (0%) | 1/288 (0.3%) | ||
| LIVER FUNCTION TEST ABNORMAL | 1/99 (1%) | 0/288 (0%) | ||
| ALANINE AMINOTRANSFERASE INCREASED | 1/99 (1%) | 0/288 (0%) | ||
| ASPARTATE AMINOTRANSFERASE INCREASED | 1/99 (1%) | 0/288 (0%) | ||
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 0/99 (0%) | 1/288 (0.3%) | ||
| ELECTROCARDIOGRAM QT CORRECTED INTERVAL | 0/99 (0%) | 0/288 (0%) | ||
| Metabolism and nutrition disorders | ||||
| ANOREXIA | 0/99 (0%) | 1/288 (0.3%) | ||
| DEHYDRATION | 1/99 (1%) | 3/288 (1%) | ||
| HYPERKALAEMIA | 0/99 (0%) | 1/288 (0.3%) | ||
| HYPERCALCAEMIA | 1/99 (1%) | 0/288 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| BACK PAIN | 0/99 (0%) | 3/288 (1%) | ||
| BONE PAIN | 0/99 (0%) | 2/288 (0.7%) | ||
| ARTHRALGIA | 0/99 (0%) | 2/288 (0.7%) | ||
| TENOSYNOVITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| RHABDOMYOLYSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| MUSCULOSKELETAL CHEST PAIN | 1/99 (1%) | 0/288 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| METASTASIS | 0/99 (0%) | 1/288 (0.3%) | ||
| SKIN CANCER | 1/99 (1%) | 1/288 (0.3%) | ||
| BREAST CANCER | 1/99 (1%) | 0/288 (0%) | ||
| ADENOCARCINOMA | 0/99 (0%) | 1/288 (0.3%) | ||
| LEIOMYOSARCOMA | 0/99 (0%) | 1/288 (0.3%) | ||
| PROSTATE CANCER | 0/99 (0%) | 1/288 (0.3%) | ||
| BASAL CELL CARCINOMA | 1/99 (1%) | 2/288 (0.7%) | ||
| MYELODYSPLASTIC SYNDROME | 0/99 (0%) | 1/288 (0.3%) | ||
| CHRONIC MYELOID LEUKAEMIA | 0/99 (0%) | 5/288 (1.7%) | ||
| CHRONIC LYMPHOCYTIC LEUKAEMIA | 1/99 (1%) | 0/288 (0%) | ||
| SQUAMOUS CELL CARCINOMA OF SKIN | 0/99 (0%) | 1/288 (0.3%) | ||
| METASTATIC SQUAMOUS CELL CARCINOMA | 0/99 (0%) | 1/288 (0.3%) | ||
| BLAST CRISIS IN MYELOGENOUS LEUKAEMIA | 0/99 (0%) | 1/288 (0.3%) | ||
| Nervous system disorders | ||||
| SYNCOPE | 0/99 (0%) | 1/288 (0.3%) | ||
| HEADACHE | 1/99 (1%) | 1/288 (0.3%) | ||
| DIZZINESS | 0/99 (0%) | 1/288 (0.3%) | ||
| CEREBRAL HAEMORRHAGE | 0/99 (0%) | 2/288 (0.7%) | ||
| NEUROPATHY PERIPHERAL | 0/99 (0%) | 1/288 (0.3%) | ||
| Psychiatric disorders | ||||
| DEPRESSION | 1/99 (1%) | 0/288 (0%) | ||
| Renal and urinary disorders | ||||
| POLLAKIURIA | 0/99 (0%) | 1/288 (0.3%) | ||
| RENAL FAILURE | 1/99 (1%) | 4/288 (1.4%) | ||
| RENAL FAILURE ACUTE | 0/99 (0%) | 2/288 (0.7%) | ||
| GLOMERULONEPHROPATHY | 0/99 (0%) | 1/288 (0.3%) | ||
| Reproductive system and breast disorders | ||||
| ENDOMETRIOSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| UTERINE HAEMORRHAGE | 0/99 (0%) | 1/288 (0.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| STRIDOR | 1/99 (1%) | 0/288 (0%) | ||
| DYSPNOEA | 8/99 (8.1%) | 15/288 (5.2%) | ||
| EPISTAXIS | 1/99 (1%) | 1/288 (0.3%) | ||
| CHYLOTHORAX | 0/99 (0%) | 1/288 (0.3%) | ||
| PNEUMONITIS | 1/99 (1%) | 2/288 (0.7%) | ||
| BRONCHOSPASM | 0/99 (0%) | 1/288 (0.3%) | ||
| LUNG DISORDER | 0/99 (0%) | 1/288 (0.3%) | ||
| PLEURAL DISORDER | 0/99 (0%) | 1/288 (0.3%) | ||
| PLEURAL EFFUSION | 16/99 (16.2%) | 32/288 (11.1%) | ||
| PULMONARY OEDEMA | 1/99 (1%) | 0/288 (0%) | ||
| LUNG INFILTRATION | 1/99 (1%) | 5/288 (1.7%) | ||
| PULMONARY EMBOLISM | 1/99 (1%) | 0/288 (0%) | ||
| DYSPNOEA EXERTIONAL | 1/99 (1%) | 0/288 (0%) | ||
| RESPIRATORY FAILURE | 0/99 (0%) | 1/288 (0.3%) | ||
| BRONCHIAL OBSTRUCTION | 1/99 (1%) | 0/288 (0%) | ||
| NASAL SEPTUM DISORDER | 0/99 (0%) | 1/288 (0.3%) | ||
| PULMONARY HYPERTENSION | 3/99 (3%) | 0/288 (0%) | ||
| INTERSTITIAL LUNG DISEASE | 0/99 (0%) | 1/288 (0.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ACNE | 1/99 (1%) | 0/288 (0%) | ||
| RASH | 0/99 (0%) | 1/288 (0.3%) | ||
| ERYTHEMA | 0/99 (0%) | 1/288 (0.3%) | ||
| PRURITUS | 0/99 (0%) | 1/288 (0.3%) | ||
| DERMATITIS | 0/99 (0%) | 1/288 (0.3%) | ||
| SKIN DISORDER | 0/99 (0%) | 1/288 (0.3%) | ||
| SKIN NECROSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| Surgical and medical procedures | ||||
| HYSTERECTOMY | 0/99 (0%) | 1/288 (0.3%) | ||
| BONE MARROW TRANSPLANT | 0/99 (0%) | 2/288 (0.7%) | ||
| CORONARY ARTERIAL STENT INSERTION | 0/99 (0%) | 1/288 (0.3%) | ||
| Vascular disorders | ||||
| EMBOLISM | 1/99 (1%) | 0/288 (0%) | ||
| HAEMATOMA | 0/99 (0%) | 2/288 (0.7%) | ||
| HYPERTENSION | 1/99 (1%) | 1/288 (0.3%) | ||
| CIRCULATORY COLLAPSE | 1/99 (1%) | 0/288 (0%) | ||
| DEEP VEIN THROMBOSIS | 0/99 (0%) | 1/288 (0.3%) | ||
| PERIPHERAL ARTERIAL OCCLUSIVE DISEASE | 0/99 (0%) | 1/288 (0.3%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Intolerant | Resistant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 96/99 (97%) | 287/288 (99.7%) | ||
| Blood and lymphatic system disorders | ||||
| ANAEMIA | 12/99 (12.1%) | 33/288 (11.5%) | ||
| NEUTROPENIA | 16/99 (16.2%) | 52/288 (18.1%) | ||
| THROMBOCYTOPENIA | 12/99 (12.1%) | 67/288 (23.3%) | ||
| Cardiac disorders | ||||
| PALPITATIONS | 6/99 (6.1%) | 16/288 (5.6%) | ||
| PERICARDIAL EFFUSION | 5/99 (5.1%) | 13/288 (4.5%) | ||
| Eye disorders | ||||
| EYELID OEDEMA | 5/99 (5.1%) | 6/288 (2.1%) | ||
| VISION BLURRED | 8/99 (8.1%) | 12/288 (4.2%) | ||
| Gastrointestinal disorders | ||||
| NAUSEA | 40/99 (40.4%) | 108/288 (37.5%) | ||
| COLITIS | 5/99 (5.1%) | 6/288 (2.1%) | ||
| VOMITING | 17/99 (17.2%) | 64/288 (22.2%) | ||
| DIARRHOEA | 44/99 (44.4%) | 153/288 (53.1%) | ||
| DYSPEPSIA | 13/99 (13.1%) | 19/288 (6.6%) | ||
| TOOTHACHE | 3/99 (3%) | 15/288 (5.2%) | ||
| FLATULENCE | 9/99 (9.1%) | 18/288 (6.3%) | ||
| STOMATITIS | 3/99 (3%) | 15/288 (5.2%) | ||
| CONSTIPATION | 8/99 (8.1%) | 54/288 (18.8%) | ||
| HAEMORRHOIDS | 11/99 (11.1%) | 17/288 (5.9%) | ||
| ABDOMINAL PAIN | 17/99 (17.2%) | 47/288 (16.3%) | ||
| MOUTH ULCERATION | 2/99 (2%) | 15/288 (5.2%) | ||
| ABDOMINAL DISTENSION | 9/99 (9.1%) | 27/288 (9.4%) | ||
| ABDOMINAL PAIN UPPER | 14/99 (14.1%) | 36/288 (12.5%) | ||
| General disorders | ||||
| PAIN | 6/99 (6.1%) | 21/288 (7.3%) | ||
| CHILLS | 10/99 (10.1%) | 31/288 (10.8%) | ||
| OEDEMA | 2/99 (2%) | 15/288 (5.2%) | ||
| FATIGUE | 48/99 (48.5%) | 136/288 (47.2%) | ||
| PYREXIA | 33/99 (33.3%) | 104/288 (36.1%) | ||
| ASTHENIA | 19/99 (19.2%) | 58/288 (20.1%) | ||
| CHEST PAIN | 17/99 (17.2%) | 35/288 (12.2%) | ||
| CHEST DISCOMFORT | 10/99 (10.1%) | 19/288 (6.6%) | ||
| OEDEMA PERIPHERAL | 24/99 (24.2%) | 75/288 (26%) | ||
| INFLUENZA LIKE ILLNESS | 3/99 (3%) | 19/288 (6.6%) | ||
| Infections and infestations | ||||
| SINUSITIS | 8/99 (8.1%) | 17/288 (5.9%) | ||
| BRONCHITIS | 8/99 (8.1%) | 23/288 (8%) | ||
| ORAL HERPES | 4/99 (4%) | 24/288 (8.3%) | ||
| NASOPHARYNGITIS | 17/99 (17.2%) | 53/288 (18.4%) | ||
| URINARY TRACT INFECTION | 4/99 (4%) | 19/288 (6.6%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 19/99 (19.2%) | 36/288 (12.5%) | ||
| Injury, poisoning and procedural complications | ||||
| CONTUSION | 5/99 (5.1%) | 21/288 (7.3%) | ||
| Investigations | ||||
| WEIGHT DECREASED | 12/99 (12.1%) | 39/288 (13.5%) | ||
| WEIGHT INCREASED | 10/99 (10.1%) | 30/288 (10.4%) | ||
| Metabolism and nutrition disorders | ||||
| ANOREXIA | 16/99 (16.2%) | 52/288 (18.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| MYALGIA | 19/99 (19.2%) | 49/288 (17%) | ||
| BACK PAIN | 19/99 (19.2%) | 53/288 (18.4%) | ||
| BONE PAIN | 10/99 (10.1%) | 48/288 (16.7%) | ||
| NECK PAIN | 4/99 (4%) | 24/288 (8.3%) | ||
| ARTHRALGIA | 15/99 (15.2%) | 86/288 (29.9%) | ||
| MUSCLE SPASMS | 10/99 (10.1%) | 27/288 (9.4%) | ||
| PAIN IN EXTREMITY | 18/99 (18.2%) | 58/288 (20.1%) | ||
| MUSCULOSKELETAL PAIN | 12/99 (12.1%) | 27/288 (9.4%) | ||
| MUSCULOSKELETAL CHEST PAIN | 5/99 (5.1%) | 17/288 (5.9%) | ||
| Nervous system disorders | ||||
| HEADACHE | 49/99 (49.5%) | 128/288 (44.4%) | ||
| DIZZINESS | 17/99 (17.2%) | 56/288 (19.4%) | ||
| DYSGEUSIA | 5/99 (5.1%) | 10/288 (3.5%) | ||
| PARAESTHESIA | 7/99 (7.1%) | 33/288 (11.5%) | ||
| Psychiatric disorders | ||||
| ANXIETY | 6/99 (6.1%) | 17/288 (5.9%) | ||
| INSOMNIA | 14/99 (14.1%) | 33/288 (11.5%) | ||
| DEPRESSION | 10/99 (10.1%) | 20/288 (6.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| COUGH | 36/99 (36.4%) | 110/288 (38.2%) | ||
| DYSPNOEA | 46/99 (46.5%) | 128/288 (44.4%) | ||
| WHEEZING | 5/99 (5.1%) | 9/288 (3.1%) | ||
| DYSPHONIA | 5/99 (5.1%) | 7/288 (2.4%) | ||
| EPISTAXIS | 3/99 (3%) | 27/288 (9.4%) | ||
| RHINORRHOEA | 5/99 (5.1%) | 9/288 (3.1%) | ||
| PLEURAL EFFUSION | 37/99 (37.4%) | 90/288 (31.3%) | ||
| DYSPNOEA EXERTIONAL | 5/99 (5.1%) | 21/288 (7.3%) | ||
| PHARYNGOLARYNGEAL PAIN | 14/99 (14.1%) | 42/288 (14.6%) | ||
| Skin and subcutaneous tissue disorders | ||||
| ACNE | 12/99 (12.1%) | 17/288 (5.9%) | ||
| RASH | 43/99 (43.4%) | 103/288 (35.8%) | ||
| ALOPECIA | 15/99 (15.2%) | 24/288 (8.3%) | ||
| DRY SKIN | 9/99 (9.1%) | 18/288 (6.3%) | ||
| ERYTHEMA | 11/99 (11.1%) | 19/288 (6.6%) | ||
| PRURITUS | 18/99 (18.2%) | 36/288 (12.5%) | ||
| URTICARIA | 5/99 (5.1%) | 10/288 (3.5%) | ||
| SKIN LESION | 9/99 (9.1%) | 18/288 (6.3%) | ||
| NIGHT SWEATS | 7/99 (7.1%) | 34/288 (11.8%) | ||
| HYPERHIDROSIS | 2/99 (2%) | 17/288 (5.9%) | ||
| PERIORBITAL OEDEMA | 13/99 (13.1%) | 28/288 (9.7%) | ||
| DERMATITIS ACNEIFORM | 7/99 (7.1%) | 9/288 (3.1%) | ||
| Vascular disorders | ||||
| FLUSHING | 9/99 (9.1%) | 14/288 (4.9%) | ||
| HOT FLUSH | 5/99 (5.1%) | 14/288 (4.9%) | ||
| HYPERTENSION | 9/99 (9.1%) | 19/288 (6.6%) | ||
Limitations/Caveats
[Not Specified]
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 | BMS Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00101660
Other Study ID Numbers:
- CA180-013
- NCT00112801
First Posted:
Jan 13, 2005
Last Update Posted:
Mar 2, 2012
Last Verified:
Feb 1, 2012