Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00123487
Collaborator
(none)
638
119
2
96
5.4
0.1
Study Details
Study Description
Brief Summary
This is a phase III study of BMS-354825 in subjects with chronic myelogenous leukemia in accelerated phase, or in myeloid or lymphoid blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia who are resistant or intolerant to imatinib mesylate (Gleevec).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
638 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Two-Arm, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects With Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
Study Start Date
:
Jun 1, 2005
Actual Primary Completion Date
:
Nov 1, 2006
Actual Study Completion Date
:
Jun 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: dasatinib Twice a Day (BID) 70 mg dasatinib twice a day (BID) |
Drug: dasatinib
Tablets, Oral, 140 mg QD, indefinitely, survival study
Other Names:
|
| Experimental: dasatinib Once a Day (QD) 140 mg dasatinib once a day (QD) |
Drug: dasatinib
Tablets, Oral, 70 mg BID, indefinitely, survival study
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population [Randomization up to 6 months]
MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm^3; platelets ≥ 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.
Secondary Outcome Measures
- Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population [Randomization up to 2 years]
A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized.
- Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population [Randomization up to 2 years]
MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm^3; platelets ≥ 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants.
- Median Time to Major Hematologic Response (MaHR) - Randomized Population [Day 1 up to 6 months (time of primary endpoint), 2 years]
A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months.
- Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study [Day 1 up to 5 years]
MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Median duration was measured in months.
- Percent of Participants With Overall Hematologic Response - Randomized Population [Randomization up to 6 Months, 2 Years]
Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. MiHR defined as: < 15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants.
- Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population [Randomization up to 6 months, 2 years]
Type of hematologic response: CHR defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and <100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Minor Hematologic Response (MiHR): <15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR.
- Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population [Randomization up to 6 Months, 2 Years]
Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants.
- Number of Participants With Best Cytogenic Response (CyR) - Randomized Population [Randomization up to 6 Months, 2 Years]
Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM.
- Median Progression Free Survival (PFS) - Randomized Population [Randomization up to 5 Years]
PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months.
- Median Overall Survival (OS) - Randomized Population [Randomization up to 5 Years]
OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months.
- Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population [24 months, 36 months, 48 months, 60 months]
PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months.
- Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants [Day 1 to Year 7]
With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0.
- Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants [Baseline to Year 2]
Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) version 3.0. CTC Grade 3 and 4 criteria are defined as follows: White blood cells (WBC): Grade (Gr) 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. Absolute neutrophil count (ANC): Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Baseline was laboratory value obtained within 2 weeks prior to randomization.
- Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations [Day 1 up to Year 7]
Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0. Grade 4 hematology evaluations used to determine myelosuppression included: WBC: <1.0*10^9/L. ANC: <0.5*10^9/L. Platelet count <25.0 to 10^9/L.
- Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants [Baseline to Year 2]
Laboratory abnormalities were graded according to the NCI CTC version 3.0. Grade 3 and 4 criteria were defined as follows: Upper limit of normal (ULN). Alanine transaminase (ALT) Grade (Gr) 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Aspartate aminotransferase (AST) Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. Serum creatinine (H) Gr 3: >3.0 to 6.0*ULN; Gr 4: >6.0*ULN. Calcium (L) Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; Phosphorus (L): Gr 3: <2.0 - 1.0 mg/dL , Gr 4: <1.0 mg/dL. Non-hematologic laboratory results were not collected beyond Year 2. Baseline values were obtained within 2 weeks prior to randomization.
- Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants [Baseline to Year 2]
A12-lead electrocardiogram (ECG) was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Days 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. The QT interval corrected with Fridericia formula is presented with categories of changes from baseline (BL) in milliseconds (msec).
- Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants [Baseline up to Year 2]
A12-lead ECG was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Day 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. QT Interval corrected with Fridericia formula was measured in msec.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.
Inclusion Criteria:
-
Patients with Philadelphia-Positive (Ph+) (or BCR/ABL+) accelerated phase chronic myeloid leukemia, Ph+ (or BCR/ABL+) blast phase chronic myeloid leukemia, or Ph+ (or BCR/ABL+) acute lymphoblastic leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate
-
Men and women, 18 years of age or older
-
Adequate hepatic function
-
Adequate renal function
-
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for a period of at least 1 month before and at least 3 months after the study in such a manner that the risk of pregnancy is minimized
-
Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2
Exclusion Criteria:
-
Women who are pregnant or breastfeeding
-
A serious uncontrolled medical disorder or active infection that would impair the ability of the subject to receive protocol therapy
-
Uncontrolled or significant cardiovascular disease
-
Medications that increase bleeding risk
-
Medications that change heart rhythms
-
Dementia or altered mental status that would prohibit the understanding or rendering of informed consent
-
History of significant bleeding disorder unrelated to CML
-
Concurrent incurable malignancy other than CML
-
Evidence of organ dysfunction or digestive dysfunction that would prevent administration of study therapy
-
Prior therapy with BMS-35425
-
Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled into this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of Alabama At Birmingham | Birmingham | Alabama | United States | 35294 |
| 2 | Loma Linda University Cancer Center | Loma Linda | California | United States | 92354 |
| 3 | Ucla Dept. Of Medicine | Los Angeles | California | United States | 90095 |
| 4 | Washington Cancer Institute At Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
| 5 | University Of Miami | Miami | Florida | United States | 33136 |
| 6 | Emory University School Of Medicine | Atlanta | Georgia | United States | 30322 |
| 7 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 8 | The University Of Chicago | Chicago | Illinois | United States | 60637-1463 |
| 9 | Indiana University Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 10 | University Of Kentucky | Lexington | Kentucky | United States | 40536-0098 |
| 11 | University Of Maryland | Baltimore | Maryland | United States | 21201-1595 |
| 12 | Dana Faber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 13 | Karmanos Cancer Center | Detroit | Michigan | United States | 48201 |
| 14 | Washington University School Of Medicine | Saint Louis | Missouri | United States | 63110-1093 |
| 15 | Nebraska Methodist Hospital | Omaha | Nebraska | United States | 68114 |
| 16 | Devetten, Marcel | Omaha | Nebraska | United States | 68198-7680 |
| 17 | The Cancer Center At Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 18 | The Cancer Institute Of New Jersey | New Brunswick | New Jersey | United States | 08903 |
| 19 | New York Presbyterian Hospital | New York | New York | United States | 10021 |
| 20 | The University Of North Carolina At Chapel Hill | Chapel Hill | North Carolina | United States | 27599-7305 |
| 21 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 22 | Oregon Health & Sci Univ | Portland | Oregon | United States | 97239 |
| 23 | Western Pennsylvania Cancer Institute | Pittsburgh | Pennsylvania | United States | 15224 |
| 24 | Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 25 | The University Of Texas Md Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 26 | Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
| 27 | Local Institution | Capital Federal | Buenos Aires | Argentina | 1280 |
| 28 | Local Institution | St Leonards | New South Wales | Australia | 2065 |
| 29 | Local Institution | South Brisbane | Queensland | Australia | 4101 |
| 30 | Local Institution | Adelaide | South Australia | Australia | SA 5000 |
| 31 | Local Institution | Parkville | Victoria | Australia | 3050 |
| 32 | Local Institution | Perth | Western Australia | Australia | WA 6000 |
| 33 | Local Institution | Wien | Austria | 1090 | |
| 34 | Local Institution | B-leuven | Belgium | 3000 | |
| 35 | Local Institution | Brugge | Belgium | 8000 | |
| 36 | Local Institution | Bruxelles | Belgium | 1000 | |
| 37 | Local Institution | Charleroi | Belgium | 6000 | |
| 38 | Local Institution | Yvoir | Belgium | 5530 | |
| 39 | Local Institution | Curitiba | Parana | Brazil | 80060-900 |
| 40 | Local Institution | Campinas | Sao Paulo | Brazil | 13083-970 |
| 41 | Local Institution | Morumbi | Sao Paulo | Brazil | 05652-000 |
| 42 | Local Institution | Rio De Janeiro | Brazil | 20230-130 | |
| 43 | Local Institution | Sao Paulo | Brazil | 05403-000 | |
| 44 | Local Institution | Edmonton | Alberta | Canada | T6G 1Z2 |
| 45 | Local Institution | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 46 | Local Institution | Montreal | Quebec | Canada | H3A 1A1 |
| 47 | Local Institution | Brno | Czech Republic | 62500 | |
| 48 | Local Institution | Prague 2 | Czech Republic | 128 20 | |
| 49 | Local Institution | Aarhus C | Denmark | 8000 | |
| 50 | Local Institution | Herlev | Denmark | 2730 | |
| 51 | Local Institution | Odense C | Denmark | 5000 | |
| 52 | Local Institution | Helsinki | Finland | 00029 | |
| 53 | Local Institution | Caen Cedex | France | 14033 | |
| 54 | Local Institution | Creteil Cedex | France | 94010 | |
| 55 | Local Institution | Grenoble Cedex 9 | France | 38043 | |
| 56 | Local Institution | Lille Cedex | France | 59037 | |
| 57 | Local Institution | Lyon Cedex | France | 69437 | |
| 58 | Local Institution | Marseille Cedex 9 | France | 13273 | |
| 59 | Local Institution | Nantes | France | 44000 | |
| 60 | Local Institution | Paris Cedex 10 | France | 75475 | |
| 61 | Local Institution | Pessac | France | 33604 | |
| 62 | Local Institution | Poitiers Cedex | France | 86021 | |
| 63 | Local Institution | Strasbourg Cedex | France | 67091 | |
| 64 | Local Institution | Dresden | Germany | 01307 | |
| 65 | Local Institution | Frankfurt | Germany | 60596 | |
| 66 | Local Institution | Hamburg | Germany | 20246 | |
| 67 | Local Institution | Leipzig | Germany | 04103 | |
| 68 | Local Institution | Mainz | Germany | 55131 | |
| 69 | Local Institution | Mannheim | Germany | 68167 | |
| 70 | Local Institution | Athens | Greece | 11523 | |
| 71 | Local Institution | Budapest | Hungary | 1135 | |
| 72 | Local Institution | Dublin | Ireland | ||
| 73 | Local Institution | Ramat-gan | Israel | 52621 | |
| 74 | Local Institution | Bari | Italy | 70124 | |
| 75 | Local Institution | Bologna | Italy | 40138 | |
| 76 | Local Institution | Monza | Italy | 20052 | |
| 77 | Local Institution | Napoli | Italy | 80131 | |
| 78 | Local Institution | Orbassano (to) | Italy | 10043 | |
| 79 | Local Institution | Roma | Italy | 00144 | |
| 80 | Local Institution | Jeollanam-do | Korea, Republic of | ||
| 81 | Local Institution | Seoul | Korea, Republic of | 110-744 | |
| 82 | Local Institution | Seoul | Korea, Republic of | 137-040 | |
| 83 | Local Institution | Seoul | Korea, Republic of | 138-736 | |
| 84 | Local Institution | Rotterdam | Netherlands | 3075 EA | |
| 85 | Local Institution | Trondheim | Norway | 7006 | |
| 86 | Local Institution | Jesus Maria | Lima | Peru | 11 |
| 87 | Local Institution | Lima | Peru | 34 | |
| 88 | Local Institution | Quezon City | Philippines | 1102 | |
| 89 | Local Institution | Gdansk | Poland | 80211 | |
| 90 | Local Institution | Katowice | Poland | 40032 | |
| 91 | Local Institution | Krakow | Poland | 31501 | |
| 92 | Local Institution | Lodz | Poland | 93510 | |
| 93 | Local Institution | Lublin | Poland | 20950 | |
| 94 | Local Institution | Warsaw | Poland | 02097 | |
| 95 | Local Institution | Moscow | Russian Federation | 125167 | |
| 96 | Local Institution | St.petersburg | Russian Federation | 197022 | |
| 97 | Local Institution | Singapore | Singapore | 169608 | |
| 98 | Local Institution | Bloemfontein | Free State | South Africa | 9301 |
| 99 | Local Institution | Groenkloof | Gauteng | South Africa | 0181 |
| 100 | Local Institution | Parktown | Gauteng | South Africa | 2193 |
| 101 | Local Institution | Observatory | Western Cape | South Africa | 7925 |
| 102 | Local Institution | Barcelona | Spain | 08036 | |
| 103 | Local Institution | Madrid | Spain | 28006 | |
| 104 | Local Institution | Madrid | Spain | 28034 | |
| 105 | Local Institution | Valencia | Spain | 46009 | |
| 106 | Local Institution | Lund | Sweden | 22185 | |
| 107 | Local Institution | Stockholm | Sweden | 17176 | |
| 108 | Local Institution | Umea | Sweden | 90185 | |
| 109 | Local Institution | Uppsala | Sweden | 75185 | |
| 110 | Local Institution | Basel | Switzerland | 4031 | |
| 111 | Local Institution | Taipei | Taiwan | 100 | |
| 112 | Local Institution | Taipei | Taiwan | ||
| 113 | Local Institution | Taoyuan | Taiwan | 333 | |
| 114 | Local Institution | Bangkok | Thailand | 10400 | |
| 115 | Local Institution | London | Greater London | United Kingdom | W12 ONN |
| 116 | Local Institution | Glasgow | Scotland | United Kingdom | G12 OXB |
| 117 | Local Institution | Newcastle | Tyne And Wear | United Kingdom | NE2 4HH |
| 118 | Local Institution | Edinburgh | United Kingdom | EH8 9RS | |
| 119 | Local Institution | Liverpool | United Kingdom | L7 8XP |
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:
NCT00123487
Other Study ID Numbers:
- CA180-035
- NCT00331396
First Posted:
Jul 25, 2005
Last Update Posted:
Nov 2, 2014
Last Verified:
Oct 1, 2014
Keywords provided by Bristol-Myers Squibb
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Study started June 2005; recruitment completed March 2006; study ended June 2013 (Year 7) when the study closed and all participants were off study treatment. Those participants who were resistant or intolerant to prior imatinib were enrolled. |
|---|---|
| Pre-assignment Detail | 638 participants were enrolled; 27 were not randomized due to: adverse event (1), death (5), other (5), poor/noncompliance (1), no longer met criteria (13), withdrew consent (2). A total of 611 were randomized to treatment; 609 were treated: 2 randomized but not treated due to death (1) and serious adverse event (1). |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. |
| Period Title: Randomized | ||
| STARTED | 306 | 305 |
| COMPLETED | 305 | 304 |
| NOT COMPLETED | 1 | 1 |
| Period Title: Randomized | ||
| STARTED | 304 | 305 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 304 | 305 |
Baseline Characteristics
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID | Total |
|---|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Total of all reporting groups |
| Overall Participants | 306 | 305 | 611 |
| Age, Customized (participants) [Number] | |||
| Less than (<) 21 years |
5
1.6%
|
4
1.3%
|
9
1.5%
|
| 21 - 45 years |
101
33%
|
83
27.2%
|
184
30.1%
|
| 46 - 65 years |
143
46.7%
|
143
46.9%
|
286
46.8%
|
| 66 - 75 years |
49
16%
|
65
21.3%
|
114
18.7%
|
| Greater than (>) 75 years |
8
2.6%
|
9
3%
|
17
2.8%
|
| Not Reported |
0
0%
|
1
0.3%
|
1
0.2%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
133
43.5%
|
134
43.9%
|
267
43.7%
|
| Male |
173
56.5%
|
171
56.1%
|
344
56.3%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| Asian |
38
12.4%
|
38
12.5%
|
76
12.4%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
1
0.3%
|
1
0.2%
|
| Black or African American |
17
5.6%
|
18
5.9%
|
35
5.7%
|
| White |
235
76.8%
|
236
77.4%
|
471
77.1%
|
| Other |
13
4.2%
|
9
3%
|
22
3.6%
|
| Unknown or Not reported |
3
1%
|
3
1%
|
6
1%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (participants) [Number] | |||
| ECOG PS 0 |
138
45.1%
|
134
43.9%
|
272
44.5%
|
| ECOG PS 1 |
121
39.5%
|
109
35.7%
|
230
37.6%
|
| ECOG PS 2 |
40
13.1%
|
58
19%
|
98
16%
|
| ECOG PS 3 |
7
2.3%
|
2
0.7%
|
9
1.5%
|
| Not Reported |
0
0%
|
2
0.7%
|
2
0.3%
|
| Imatinib Status (participants) [Number] | |||
| Primary Resistance |
43
14.1%
|
49
16.1%
|
92
15.1%
|
| Acquired Resistance |
192
62.7%
|
190
62.3%
|
382
62.5%
|
| Intolerance |
67
21.9%
|
65
21.3%
|
132
21.6%
|
| Missing |
4
1.3%
|
1
0.3%
|
5
0.8%
|
| Participants by Disease Phase (participants) [Number] | |||
| Accelerated Phase CML |
158
51.6%
|
159
52.1%
|
317
51.9%
|
| Blast Phase CML - Myeloid |
75
24.5%
|
74
24.3%
|
149
24.4%
|
| Blast Phase CML - Lymphoid |
33
10.8%
|
28
9.2%
|
61
10%
|
| Ph+ ALL |
40
13.1%
|
44
14.4%
|
84
13.7%
|
Outcome Measures
| Title | Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population |
|---|---|
| Description | MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm^3; platelets ≥ 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants. |
| Time Frame | Randomization up to 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive (not what they actually received). 95% exact confidence interval (CI) presented. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Number (95% Confidence Interval) [percentage of participants] |
48.0
15.7%
|
47.9
15.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Dasatinib 140 mg QD, Dasatinib 70 mg BID |
|---|---|---|
| Comments | Primary endpoint was to be assessed at 6-Months: Assuming a 45% MaHR rate in the 70 mg BID participants, the primary efficacy analysis required a total of 540 participants, approximately 270 in each dosing schedule, giving at least 80% power to deduce non-inferiority of the QD schedule relative to the BID schedule if the lower bound of the 95% CI for the difference in MaHR rates (MaHRRQD - MaHRRBID) is greater than -12%. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Non-inferiority of the QD schedule relative to the BID schedule was claimed if the lower bound of the 95% CI for difference (QD - BD) was ≥ -12%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent Difference |
| Estimated Value | 0.2 | |
| Confidence Interval |
(2-Sided) 95% -7.8 to 8.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population |
|---|---|
| Description | A MaHR was defined as a participant having either CHR or NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percent: number of participants with MaHR /number of participants randomized. |
| Time Frame | Randomization up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Number (95% Confidence Interval) [percentage of participants] |
50.7
16.6%
|
49.8
16.3%
|
| Title | Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population |
|---|---|
| Description | MaHR was defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm^3; platelets ≥ 100,000/mm^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; <5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one parameter of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule.. Percentage: participants with MaHR/randomized participants. |
| Time Frame | Randomization up to 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. n=number of participants in disease group. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. |
| Measure Participants | 306 | 305 |
| Accelerated Phase (n=158, 159) |
66.5
21.7%
|
67.9
22.3%
|
| Myeloid Blast Phase (n=75,74) |
28.0
9.2%
|
28.4
9.3%
|
| Lymphoid Blast Phase (n=33,28) |
42.4
13.9%
|
32.1
10.5%
|
| Ph+ Acute Lymphoblastic Leukemia (n=40,44) |
37.5
12.3%
|
31.8
10.4%
|
| Title | Median Time to Major Hematologic Response (MaHR) - Randomized Population |
|---|---|
| Description | A participants' time to MaHR was defined as the time from the first dosing date until criteria are first met for CHR or NEL, whichever occurred first. Non-responders were censored at the maximum of the date of last hematologic or cytogenetic assessment. Median time was measured in months. |
| Time Frame | Day 1 up to 6 months (time of primary endpoint), 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| 6 Months |
1.9
|
1.9
|
| 2 Years |
1.9
|
1.9
|
| Title | Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study |
|---|---|
| Description | MaHR was defined by either CHR or no evidence of leukemia NEL. CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Median duration was measured in months. |
| Time Frame | Day 1 up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who achieved a MaHR during the study. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 156 | 153 |
| Median (95% Confidence Interval) [Months] |
21.1
|
24.7
|
| Title | Percent of Participants With Overall Hematologic Response - Randomized Population |
|---|---|
| Description | Overall Hematologic Response (OHR) was defined as CHR, NEL or minor hematologic response (MiHR). CHR was defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and < 100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. MiHR defined as: < 15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Percentage: participants with OHR/ randomized participants. |
| Time Frame | Randomization up to 6 Months, 2 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| 6 Months |
59.2
19.3%
|
57.4
18.8%
|
| 2 Years |
60.1
19.6%
|
59.0
19.3%
|
| Title | Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population |
|---|---|
| Description | Type of hematologic response: CHR defined as: WBC ≤ ULN; ANC ≥ 1,000/mm^3; - platelets ≥ 100,000/mm^3; - no blasts or promyelocytes in PB; BM blasts ≤ 5%; < 5% myelocytes plus metamyelocytes in PB; basophils in PB < 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by the same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm^3 and <100,000/mm^3; ANC > 500/mm^3 and <1,000/mm^3. Minor Hematologic Response (MiHR): <15% blasts in BM and in PB; < 30% blasts + promyelocytes in BM and PB; < 20% basophils in PB; No extra-medullary disease other than spleen and liver. Major hematologic response (MaHR ) was CHR or NEL. Overall hematologic response was CHR or NEL or MiHR. |
| Time Frame | Randomization up to 6 months, 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Complete Response, 6 months |
94
30.7%
|
96
31.5%
|
| Complete Response, 2 years |
108
35.3%
|
110
36.1%
|
| No Evidence of Leukemia, 6 months |
53
17.3%
|
50
16.4%
|
| No Evidence of Leukemia, 2 years |
47
15.4%
|
42
13.8%
|
| Minor Response, 6 months |
34
11.1%
|
29
9.5%
|
| Minor Response, 2 years |
29
9.5%
|
28
9.2%
|
| No Response, 6 months |
125
40.8%
|
130
42.6%
|
| No Response, 2 years |
122
39.9%
|
125
41%
|
| MaHR, 6 months |
147
48%
|
146
47.9%
|
| MaHR, 2 years |
155
50.7%
|
152
49.8%
|
| Overall Response, 6 months |
181
59.2%
|
175
57.4%
|
| Overall Response, 2 years |
184
60.1%
|
180
59%
|
| Title | Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population |
|---|---|
| Description | Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM; Major cytogenetic response (MCyR) was defined as CCyR or PCyR. Percentage: number of participants with MCyR and denominator is number of randomized participants. |
| Time Frame | Randomization up to 6 Months, 2 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| 6 Months |
36.9
12.1%
|
39.3
12.9%
|
| 2 Years |
41.5
13.6%
|
41.3
13.5%
|
| Title | Number of Participants With Best Cytogenic Response (CyR) - Randomized Population |
|---|---|
| Description | Cytogenetic assessments were performed only for the first 2 years of study. CyR was based on the number of Ph+ metaphases among cells in metaphase on a BM sample. The criteria for CyR were as follows: Complete cytogenetic response (CCyR): 0% Ph+ cells in metaphase in BM; Partial cytogenetic response (PCyR): 1% to 35% Ph+ cells in metaphase in BM; Minor cytogenetic response: 36% to 65% Ph+ cells in metaphase in BM; Minimal cytogenetic response: 66% to 95% Ph+ cells in metaphase in BM; No cytogenetic response: 96% to 100% Ph+ cells in metaphase in BM. |
| Time Frame | Randomization up to 6 Months, 2 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Complete CyR, 6 months |
89
29.1%
|
84
27.5%
|
| Complete CyR, 2 years |
97
31.7%
|
98
32.1%
|
| Partial CyR, 6 months |
24
7.8%
|
36
11.8%
|
| Partial CyR, 2 years |
30
9.8%
|
28
9.2%
|
| Minor CyR, 6 months |
19
6.2%
|
18
5.9%
|
| Minor CyR, 2 years |
13
4.2%
|
16
5.2%
|
| Minimal CyR, 6 months |
47
15.4%
|
45
14.8%
|
| Minimal CyR, 2 years |
43
14.1%
|
40
13.1%
|
| No response, 6 months |
63
20.6%
|
56
18.4%
|
| No response, 2 years |
60
19.6%
|
51
16.7%
|
| Unable to determine, 6 months |
64
20.9%
|
66
21.6%
|
| Unable to determine, 2 years |
63
20.6%
|
72
23.6%
|
| Title | Median Progression Free Survival (PFS) - Randomized Population |
|---|---|
| Description | PFS was defined as: Time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. Median duration was measured in months. |
| Time Frame | Randomization up to 5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Median (95% Confidence Interval) [Months] |
7.8
|
10.4
|
| Title | Median Overall Survival (OS) - Randomized Population |
|---|---|
| Description | OS was defined as time from randomization until date of death. Participants who had not died or who were lost to follow-up were censored on the last date on which the participant was known to be alive. Median duration was measured in months. |
| Time Frame | Randomization up to 5 Years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| Median (95% Confidence Interval) [Months] |
17.7
|
22.4
|
| Title | Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population |
|---|---|
| Description | PFS was defined as time from randomization until any of the following: Progression of disease (per investigator), or death. For those with blast phase CML or Ph+ ALL, disease progression was: loss of OHR; no decrease from on-study baseline percent blasts in PB or BM on all assessments over a 4-week period after starting maximum dose; absolute increase of at least 50% in PB blast count over a 2-week period after starting maximum dose. For those with accelerated phase CML: the list above also included: Development of blast phase CML at any time after initiation of therapy and development of extra-medullary sites other than spleen or liver. Participants who neither progressed nor died were censored on the date of their last cytogenetic or hematologic assessment. OS was defined as time from randomization until date of death. Participants who had not died or were lost to follow-up were censored on the last date they were known to be alive. Median duration was measured in months. |
| Time Frame | 24 months, 36 months, 48 months, 60 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants were analyzed based on the treatment they were randomized to receive. Kaplan-Meir estimates of PFS or OS (95% Confidence Interval) are provided below. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 306 | 305 |
| PFS at 24 Months |
29.5
9.6%
|
33.1
10.9%
|
| PFS at 36 Months |
24.1
7.9%
|
26.6
8.7%
|
| PFS at 48 Months |
19.8
6.5%
|
20.5
6.7%
|
| PFS at 60 Months |
16.9
5.5%
|
15.9
5.2%
|
| OS at 24 Months |
43.3
14.2%
|
48.7
16%
|
| OS at 36 Months |
37.1
12.1%
|
42.5
13.9%
|
| OS at 48 Months |
32.7
10.7%
|
38.2
12.5%
|
| OS at 60 Months |
28.8
9.4%
|
36.1
11.8%
|
| Title | Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants |
|---|---|
| Description | With protocol Amendment 6, the duration of the study was extended for 2 additional years (7 years total) for participants who continued to have clinical benefit and no feasible alternate access to dasatinib. However, after Year 5 the requirement to follow participants for survival and to collect other efficacy data was removed from the protocol for the remainder of the study. Only AEs and SAEs were collected up to Year 7. On-study AEs and SAEs were graded by severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The investigator AE terms were coded and grouped by preferred term and system organ class using the Medical Dictionary for Regulatory Activities (MedDRA), version 16.0. |
| Time Frame | Day 1 to Year 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 304 | 305 |
| Deaths |
203
66.3%
|
186
61%
|
| Death within 30 Days |
66
21.6%
|
63
20.7%
|
| SAEs |
228
74.5%
|
236
77.4%
|
| AEs Leading to Discontinuation |
118
38.6%
|
114
37.4%
|
| Drug-related Fluid Retention |
109
35.6%
|
137
44.9%
|
| Title | Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants |
|---|---|
| Description | Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) version 3.0. CTC Grade 3 and 4 criteria are defined as follows: White blood cells (WBC): Grade (Gr) 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. Absolute neutrophil count (ANC): Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL. Baseline was laboratory value obtained within 2 weeks prior to randomization. |
| Time Frame | Baseline to Year 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. Those participants who did not have a parameter reported at baseline are indicated. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 304 | 305 |
| WBC |
129
42.2%
|
114
37.4%
|
| WBC not reported at baseline |
2
0.7%
|
2
0.7%
|
| Platelets |
64
20.9%
|
79
25.9%
|
| Platelets not reported at baseline |
2
0.7%
|
2
0.7%
|
| Hemoglobin |
12
3.9%
|
13
4.3%
|
| Hemoglobin not reported at baseline |
2
0.7%
|
2
0.7%
|
| ANC |
127
41.5%
|
143
46.9%
|
| ANC not reported at baseline |
9
2.9%
|
8
2.6%
|
| Title | Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations |
|---|---|
| Description | Laboratory abnormalities were graded according to the National Cancer Institute Common Terminology Criteria (NCI CTC) Version 3.0. Grade 4 hematology evaluations used to determine myelosuppression included: WBC: <1.0*10^9/L. ANC: <0.5*10^9/L. Platelet count <25.0 to 10^9/L. |
| Time Frame | Day 1 up to Year 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had laboratory evaluations available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. |
| Measure Participants | 299 | 303 |
| WBC (n=299, 303) |
64
20.9%
|
72
23.6%
|
| Platelets(n=299, 303) |
167
54.6%
|
164
53.8%
|
| ANC (n=299, 303) |
132
43.1%
|
142
46.6%
|
| Title | Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants |
|---|---|
| Description | Laboratory abnormalities were graded according to the NCI CTC version 3.0. Grade 3 and 4 criteria were defined as follows: Upper limit of normal (ULN). Alanine transaminase (ALT) Grade (Gr) 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Aspartate aminotransferase (AST) Gr 3: >5.0 to 20.0*ULN; Gr 4: >20.0*ULN. Total bilirubin Gr 3: >3.0 to 10..0*ULN; Gr 4: >10.0.0*ULN. Serum creatinine (H) Gr 3: >3.0 to 6.0*ULN; Gr 4: >6.0*ULN. Calcium (L) Gr3: 6.0-7.0; Gr 4: <6.0 mg/dL; Phosphorus (L): Gr 3: <2.0 - 1.0 mg/dL , Gr 4: <1.0 mg/dL. Non-hematologic laboratory results were not collected beyond Year 2. Baseline values were obtained within 2 weeks prior to randomization. |
| Time Frame | Baseline to Year 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. Participants who did not have a parameter reported at baseline are indicated. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 304 | 305 |
| Hypophosphatemia |
28
9.2%
|
26
8.5%
|
| Phosphorus not reported at baseline |
14
4.6%
|
20
6.6%
|
| Hypocalcemia |
14
4.6%
|
9
3%
|
| Calcium not reported at baseline |
5
1.6%
|
13
4.3%
|
| Elevated ALT |
8
2.6%
|
4
1.3%
|
| ALT not reported at baseline |
4
1.3%
|
4
1.3%
|
| Elevated AST |
3
1%
|
2
0.7%
|
| AST not reported at baseline |
3
1%
|
6
2%
|
| Elevated Bilirubin |
4
1.3%
|
3
1%
|
| Bilirubin not reported at baseline |
2
0.7%
|
7
2.3%
|
| Elevated Serum Creatinine |
4
1.3%
|
2
0.7%
|
| Serum Creatinine not reported at baseline |
1
0.3%
|
3
1%
|
| Title | Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants |
|---|---|
| Description | A12-lead electrocardiogram (ECG) was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Days 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. The QT interval corrected with Fridericia formula is presented with categories of changes from baseline (BL) in milliseconds (msec). |
| Time Frame | Baseline to Year 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had appropriate baseline and on-study ECG data available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 269 | 257 |
| QTcF <-60 msec change from BL |
4
1.3%
|
7
2.3%
|
| -60 - < -30 msec change from BL |
13
4.2%
|
15
4.9%
|
| -30 - < 0 msec change from BL |
88
28.8%
|
65
21.3%
|
| 0 - 30 msec change from BL |
114
37.3%
|
125
41%
|
| > 30 - 60 msec change from BL |
31
10.1%
|
24
7.9%
|
| > 60 msec change from BL |
19
6.2%
|
21
6.9%
|
| Title | Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants |
|---|---|
| Description | A12-lead ECG was obtained at baseline (baseline=within 2 weeks prior to randomization) and once between Day 8 and 29. Additional ECGs were done at the Investigator's discretion. ECGs were read centrally. QT Interval corrected with Fridericia formula was measured in msec. |
| Time Frame | Baseline up to Year 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug and had appropriate ECG data available were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. |
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID |
|---|---|---|
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant.. |
| Measure Participants | 280 | 270 |
| Maximum QTcF Interval < 450 msec |
252
82.4%
|
239
78.4%
|
| Maximum QTcF Interval 450 - 500 msec |
21
6.9%
|
26
8.5%
|
| Maximum QTcF Interval > 500 msec |
7
2.3%
|
5
1.6%
|
Adverse Events
| Time Frame | Day 1 up to 7 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Participants who received at least one dose of study drug were analyzed. Participants were analyzed based on the treatment they actually received, not what they were randomized to receive. | |||
| Arm/Group Title | Dasatinib 140 mg QD | Dasatinib 70 mg BID | ||
| Arm/Group Description | Dasatinib was administered orally at a dose of 140 mg once a day (QD) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | Dasatinib was administered orally at a dose of 70 mg twice a day (BID) until disease progression, drug toxicity, withdrawal of consent, investigator or sponsor decision, pregnancy, or decision to do stem cell transplant. | ||
All Cause Mortality |
||||
| Dasatinib 140 mg QD | Dasatinib 70 mg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Dasatinib 140 mg QD | Dasatinib 70 mg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 228/304 (75%) | 236/305 (77.4%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 28/304 (9.2%) | 29/305 (9.5%) | ||
| Leukopenia | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Neutropenia | 9/304 (3%) | 8/305 (2.6%) | ||
| Splenomegaly | 0/304 (0%) | 1/305 (0.3%) | ||
| Leukocytosis | 7/304 (2.3%) | 5/305 (1.6%) | ||
| Pancytopenia | 0/304 (0%) | 8/305 (2.6%) | ||
| Anaemia | 12/304 (3.9%) | 25/305 (8.2%) | ||
| Thrombocytopenia | 20/304 (6.6%) | 27/305 (8.9%) | ||
| Cardiac disorders | ||||
| Left ventricular dysfunction | 0/304 (0%) | 2/305 (0.7%) | ||
| Systolic dysfunction | 0/304 (0%) | 1/305 (0.3%) | ||
| Ventricular fibrillation | 0/304 (0%) | 1/305 (0.3%) | ||
| Atrial fibrillation | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Cardio-respiratory arrest | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Cardiogenic shock | 0/304 (0%) | 1/305 (0.3%) | ||
| Pericarditis | 2/304 (0.7%) | 0/305 (0%) | ||
| Sinus bradycardia | 1/304 (0.3%) | 0/305 (0%) | ||
| Angina pectoris | 1/304 (0.3%) | 0/305 (0%) | ||
| Diastolic dysfunction | 0/304 (0%) | 2/305 (0.7%) | ||
| Myocardial infarction | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Arrhythmia | 1/304 (0.3%) | 0/305 (0%) | ||
| Cardiac failure | 1/304 (0.3%) | 3/305 (1%) | ||
| Tachycardia | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Cardiac arrest | 0/304 (0%) | 2/305 (0.7%) | ||
| Myocarditis | 0/304 (0%) | 1/305 (0.3%) | ||
| Cardiac failure congestive | 3/304 (1%) | 1/305 (0.3%) | ||
| Pericardial effusion | 3/304 (1%) | 5/305 (1.6%) | ||
| Supraventricular tachycardia | 0/304 (0%) | 2/305 (0.7%) | ||
| Congenital, familial and genetic disorders | ||||
| Aplasia | 1/304 (0.3%) | 0/305 (0%) | ||
| Ear and labyrinth disorders | ||||
| Vertigo | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 0/304 (0%) | 1/305 (0.3%) | ||
| Eye disorders | ||||
| Eye haemorrhage | 1/304 (0.3%) | 0/305 (0%) | ||
| Photophobia | 0/304 (0%) | 1/305 (0.3%) | ||
| Cataract | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Visual acuity reduced | 1/304 (0.3%) | 0/305 (0%) | ||
| Gastrointestinal disorders | ||||
| Dental caries | 0/304 (0%) | 1/305 (0.3%) | ||
| Gastrointestinal pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Intestinal ischaemia | 1/304 (0.3%) | 0/305 (0%) | ||
| Oesophageal haemorrhage | 1/304 (0.3%) | 0/305 (0%) | ||
| Abdominal pain upper | 0/304 (0%) | 2/305 (0.7%) | ||
| Diarrhoea haemorrhagic | 1/304 (0.3%) | 0/305 (0%) | ||
| Gingival pain | 0/304 (0%) | 1/305 (0.3%) | ||
| Intestinal haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Rectal polyp | 1/304 (0.3%) | 0/305 (0%) | ||
| Anal fistula | 1/304 (0.3%) | 0/305 (0%) | ||
| Anal ulcer | 0/304 (0%) | 1/305 (0.3%) | ||
| Duodenal ulcer haemorrhage | 1/304 (0.3%) | 0/305 (0%) | ||
| Nausea | 3/304 (1%) | 5/305 (1.6%) | ||
| Upper gastrointestinal haemorrhage | 2/304 (0.7%) | 2/305 (0.7%) | ||
| Vomiting | 5/304 (1.6%) | 9/305 (3%) | ||
| Colitis ischaemic | 2/304 (0.7%) | 0/305 (0%) | ||
| Haematochezia | 1/304 (0.3%) | 0/305 (0%) | ||
| Lower gastrointestinal haemorrhage | 3/304 (1%) | 4/305 (1.3%) | ||
| Rectal haemorrhage | 1/304 (0.3%) | 8/305 (2.6%) | ||
| Abdominal pain | 6/304 (2%) | 4/305 (1.3%) | ||
| Anal fissure | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Dysphagia | 0/304 (0%) | 1/305 (0.3%) | ||
| Gastric disorder | 0/304 (0%) | 1/305 (0.3%) | ||
| Gingival bleeding | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Large intestinal haemorrhage | 2/304 (0.7%) | 0/305 (0%) | ||
| Mouth ulceration | 0/304 (0%) | 1/305 (0.3%) | ||
| Oesophageal ulcer | 0/304 (0%) | 1/305 (0.3%) | ||
| Oesophagitis | 0/304 (0%) | 1/305 (0.3%) | ||
| Acute abdomen | 0/304 (0%) | 1/305 (0.3%) | ||
| Diarrhoea | 14/304 (4.6%) | 15/305 (4.9%) | ||
| Faecaloma | 1/304 (0.3%) | 0/305 (0%) | ||
| Gastric haemorrhage | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Gastritis erosive | 1/304 (0.3%) | 0/305 (0%) | ||
| Gastrointestinal disorder | 1/304 (0.3%) | 0/305 (0%) | ||
| Gastrointestinal haemorrhage | 12/304 (3.9%) | 13/305 (4.3%) | ||
| Gastrointestinal ulcer | 1/304 (0.3%) | 0/305 (0%) | ||
| Melaena | 1/304 (0.3%) | 0/305 (0%) | ||
| Small intestinal obstruction | 0/304 (0%) | 1/305 (0.3%) | ||
| Toothache | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Ascites | 0/304 (0%) | 1/305 (0.3%) | ||
| Diverticulum | 0/304 (0%) | 1/305 (0.3%) | ||
| Gingival swelling | 0/304 (0%) | 1/305 (0.3%) | ||
| Abdominal distension | 0/304 (0%) | 1/305 (0.3%) | ||
| Caecitis | 1/304 (0.3%) | 0/305 (0%) | ||
| Colitis | 7/304 (2.3%) | 5/305 (1.6%) | ||
| Enteritis | 2/304 (0.7%) | 0/305 (0%) | ||
| Gastritis | 1/304 (0.3%) | 0/305 (0%) | ||
| Haemorrhoids | 1/304 (0.3%) | 0/305 (0%) | ||
| Oral pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Pancreatitis | 2/304 (0.7%) | 0/305 (0%) | ||
| General disorders | ||||
| Chills | 0/304 (0%) | 3/305 (1%) | ||
| Chest pain | 0/304 (0%) | 3/305 (1%) | ||
| Generalised oedema | 0/304 (0%) | 2/305 (0.7%) | ||
| Hernia obstructive | 1/304 (0.3%) | 0/305 (0%) | ||
| Fatigue | 4/304 (1.3%) | 2/305 (0.7%) | ||
| General physical health deterioration | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Non-cardiac chest pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Pain | 2/304 (0.7%) | 0/305 (0%) | ||
| Death | 4/304 (1.3%) | 3/305 (1%) | ||
| Mucosal inflammation | 1/304 (0.3%) | 0/305 (0%) | ||
| Pyrexia | 20/304 (6.6%) | 38/305 (12.5%) | ||
| Disease progression | 2/304 (0.7%) | 2/305 (0.7%) | ||
| Influenza like illness | 1/304 (0.3%) | 0/305 (0%) | ||
| Malaise | 0/304 (0%) | 1/305 (0.3%) | ||
| Sudden death | 2/304 (0.7%) | 0/305 (0%) | ||
| Effusion | 0/304 (0%) | 1/305 (0.3%) | ||
| No therapeutic response | 0/304 (0%) | 1/305 (0.3%) | ||
| Oedema peripheral | 0/304 (0%) | 2/305 (0.7%) | ||
| Asthenia | 5/304 (1.6%) | 2/305 (0.7%) | ||
| Multi-organ failure | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Hepatobiliary disorders | ||||
| Cholelithiasis | 0/304 (0%) | 1/305 (0.3%) | ||
| Cholecystitis | 1/304 (0.3%) | 0/305 (0%) | ||
| Cholecystitis acute | 0/304 (0%) | 1/305 (0.3%) | ||
| Hyperbilirubinaemia | 0/304 (0%) | 1/305 (0.3%) | ||
| Gallbladder pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Jaundice | 0/304 (0%) | 1/305 (0.3%) | ||
| Immune system disorders | ||||
| Drug hypersensitivity | 0/304 (0%) | 1/305 (0.3%) | ||
| Graft versus host disease | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Infections and infestations | ||||
| Atypical pneumonia | 0/304 (0%) | 1/305 (0.3%) | ||
| Bacterial sepsis | 0/304 (0%) | 3/305 (1%) | ||
| Cystitis | 3/304 (1%) | 1/305 (0.3%) | ||
| Influenza | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Lower respiratory tract infection | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Lung abscess | 0/304 (0%) | 1/305 (0.3%) | ||
| Pneumonia | 26/304 (8.6%) | 27/305 (8.9%) | ||
| Pseudomonal sepsis | 1/304 (0.3%) | 0/305 (0%) | ||
| Systemic mycosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Enterococcal bacteraemia | 1/304 (0.3%) | 0/305 (0%) | ||
| Gastrointestinal infection | 2/304 (0.7%) | 0/305 (0%) | ||
| Liver abscess | 1/304 (0.3%) | 0/305 (0%) | ||
| Meningitis | 1/304 (0.3%) | 0/305 (0%) | ||
| Otitis media | 1/304 (0.3%) | 0/305 (0%) | ||
| Pseudomembranous colitis | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Septic shock | 3/304 (1%) | 4/305 (1.3%) | ||
| Staphylococcal bacteraemia | 0/304 (0%) | 3/305 (1%) | ||
| Staphylococcal infection | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Abscess limb | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Anal abscess | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Enterocolitis infectious | 0/304 (0%) | 2/305 (0.7%) | ||
| Febrile infection | 1/304 (0.3%) | 0/305 (0%) | ||
| Infection | 15/304 (4.9%) | 9/305 (3%) | ||
| Pneumonia cytomegaloviral | 0/304 (0%) | 1/305 (0.3%) | ||
| Sepsis | 5/304 (1.6%) | 15/305 (4.9%) | ||
| Viral infection | 1/304 (0.3%) | 0/305 (0%) | ||
| Abscess oral | 1/304 (0.3%) | 0/305 (0%) | ||
| Appendicitis | 2/304 (0.7%) | 0/305 (0%) | ||
| Device related infection | 4/304 (1.3%) | 3/305 (1%) | ||
| Diverticulitis | 0/304 (0%) | 2/305 (0.7%) | ||
| Erysipelas | 1/304 (0.3%) | 0/305 (0%) | ||
| Oral infection | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Anal infection | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Arthritis infective | 1/304 (0.3%) | 0/305 (0%) | ||
| Bacteraemia | 2/304 (0.7%) | 3/305 (1%) | ||
| Haemorrhoid infection | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Lobar pneumonia | 0/304 (0%) | 2/305 (0.7%) | ||
| Neutropenic sepsis | 3/304 (1%) | 2/305 (0.7%) | ||
| Osteomyelitis | 1/304 (0.3%) | 0/305 (0%) | ||
| Pharyngeal abscess | 0/304 (0%) | 1/305 (0.3%) | ||
| Skin infection | 1/304 (0.3%) | 0/305 (0%) | ||
| Tooth infection | 0/304 (0%) | 2/305 (0.7%) | ||
| Cellulitis | 5/304 (1.6%) | 2/305 (0.7%) | ||
| Device related sepsis | 0/304 (0%) | 1/305 (0.3%) | ||
| Pneumonia legionella | 0/304 (0%) | 1/305 (0.3%) | ||
| Pulmonary tuberculosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Pyelonephritis | 0/304 (0%) | 1/305 (0.3%) | ||
| Rectal abscess | 0/304 (0%) | 1/305 (0.3%) | ||
| Aspergillus infection | 1/304 (0.3%) | 0/305 (0%) | ||
| Cytomegalovirus infection | 1/304 (0.3%) | 2/305 (0.7%) | ||
| Gangrene | 1/304 (0.3%) | 0/305 (0%) | ||
| Localised infection | 0/304 (0%) | 1/305 (0.3%) | ||
| Sinusitis | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Tonsillitis | 0/304 (0%) | 1/305 (0.3%) | ||
| Central nervous system infection | 0/304 (0%) | 1/305 (0.3%) | ||
| Gastroenteritis | 1/304 (0.3%) | 4/305 (1.3%) | ||
| Herpes zoster | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Lung infection | 2/304 (0.7%) | 4/305 (1.3%) | ||
| Sinusitis aspergillus | 1/304 (0.3%) | 0/305 (0%) | ||
| Upper respiratory tract infection | 1/304 (0.3%) | 0/305 (0%) | ||
| Urinary tract infection | 4/304 (1.3%) | 3/305 (1%) | ||
| Varicella | 1/304 (0.3%) | 0/305 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Skull fracture | 1/304 (0.3%) | 0/305 (0%) | ||
| Hip fracture | 1/304 (0.3%) | 0/305 (0%) | ||
| Subdural haematoma | 1/304 (0.3%) | 4/305 (1.3%) | ||
| Wrist fracture | 1/304 (0.3%) | 0/305 (0%) | ||
| Overdose | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Procedural pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Upper limb fracture | 1/304 (0.3%) | 0/305 (0%) | ||
| Patella fracture | 0/304 (0%) | 1/305 (0.3%) | ||
| Splenic rupture | 0/304 (0%) | 2/305 (0.7%) | ||
| Sternal fracture | 1/304 (0.3%) | 0/305 (0%) | ||
| Procedural complication | 0/304 (0%) | 1/305 (0.3%) | ||
| Subdural haemorrhage | 0/304 (0%) | 2/305 (0.7%) | ||
| Tibia fracture | 0/304 (0%) | 1/305 (0.3%) | ||
| Transfusion-related acute lung injury | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Investigations | ||||
| Alanine aminotransferase | 1/304 (0.3%) | 0/305 (0%) | ||
| Biopsy lymph gland | 0/304 (0%) | 1/305 (0.3%) | ||
| Platelet count decreased | 1/304 (0.3%) | 3/305 (1%) | ||
| Troponin T increased | 1/304 (0.3%) | 0/305 (0%) | ||
| Neutrophil count | 0/304 (0%) | 1/305 (0.3%) | ||
| White blood cell count increased | 1/304 (0.3%) | 2/305 (0.7%) | ||
| Blast cell count increased | 2/304 (0.7%) | 3/305 (1%) | ||
| Blood creatinine | 0/304 (0%) | 1/305 (0.3%) | ||
| Granulocyte count | 0/304 (0%) | 1/305 (0.3%) | ||
| Aspartate aminotransferase | 1/304 (0.3%) | 0/305 (0%) | ||
| Streptococcus test positive | 0/304 (0%) | 1/305 (0.3%) | ||
| Corynebacterium test positive | 0/304 (0%) | 1/305 (0.3%) | ||
| Haemoglobin | 3/304 (1%) | 3/305 (1%) | ||
| Neutrophil count decreased | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Electrocardiogram QT prolonged | 0/304 (0%) | 1/305 (0.3%) | ||
| Haemoglobin decreased | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Platelet count | 2/304 (0.7%) | 6/305 (2%) | ||
| Transaminases increased | 1/304 (0.3%) | 0/305 (0%) | ||
| Blood creatinine increased | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Blood potassium decreased | 0/304 (0%) | 1/305 (0.3%) | ||
| Troponin increased | 1/304 (0.3%) | 0/305 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Hyperkalaemia | 1/304 (0.3%) | 0/305 (0%) | ||
| Hypocalcaemia | 1/304 (0.3%) | 0/305 (0%) | ||
| Fluid overload | 1/304 (0.3%) | 0/305 (0%) | ||
| Hyponatraemia | 0/304 (0%) | 2/305 (0.7%) | ||
| Decreased appetite | 0/304 (0%) | 1/305 (0.3%) | ||
| Fluid retention | 0/304 (0%) | 1/305 (0.3%) | ||
| Dehydration | 3/304 (1%) | 2/305 (0.7%) | ||
| Glucose tolerance impaired | 1/304 (0.3%) | 0/305 (0%) | ||
| Hypokalaemia | 2/304 (0.7%) | 0/305 (0%) | ||
| Tumour lysis syndrome | 0/304 (0%) | 1/305 (0.3%) | ||
| Hypoglycaemia | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 6/304 (2%) | 5/305 (1.6%) | ||
| Pain in extremity | 2/304 (0.7%) | 3/305 (1%) | ||
| Musculoskeletal chest pain | 0/304 (0%) | 1/305 (0.3%) | ||
| Osteonecrosis | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Rhabdomyolysis | 2/304 (0.7%) | 0/305 (0%) | ||
| Joint ankylosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Arthralgia | 4/304 (1.3%) | 2/305 (0.7%) | ||
| Rheumatoid arthritis | 0/304 (0%) | 1/305 (0.3%) | ||
| Soft tissue disorder | 1/304 (0.3%) | 0/305 (0%) | ||
| Back pain | 4/304 (1.3%) | 4/305 (1.3%) | ||
| Musculoskeletal pain | 0/304 (0%) | 1/305 (0.3%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenocarcinoma of colon | 0/304 (0%) | 1/305 (0.3%) | ||
| Blast cell proliferation | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Brain neoplasm | 0/304 (0%) | 1/305 (0.3%) | ||
| Acute lymphocytic leukaemia recurrent | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Blast crisis in myelogenous leukaemia | 9/304 (3%) | 8/305 (2.6%) | ||
| Myelodysplastic syndrome | 0/304 (0%) | 1/305 (0.3%) | ||
| Leukaemic infiltration brain | 3/304 (1%) | 1/305 (0.3%) | ||
| Lipoma | 1/304 (0.3%) | 0/305 (0%) | ||
| Squamous cell carcinoma of skin | 1/304 (0.3%) | 0/305 (0%) | ||
| Chloroma | 1/304 (0.3%) | 0/305 (0%) | ||
| Metastases to meninges | 1/304 (0.3%) | 0/305 (0%) | ||
| Metastatic neoplasm | 1/304 (0.3%) | 0/305 (0%) | ||
| Rectal cancer | 0/304 (0%) | 1/305 (0.3%) | ||
| Squamous cell carcinoma of the oral cavity | 1/304 (0.3%) | 0/305 (0%) | ||
| Thymoma | 0/304 (0%) | 1/305 (0.3%) | ||
| Acute lymphocytic leukaemia | 5/304 (1.6%) | 5/305 (1.6%) | ||
| Squamous cell carcinoma | 3/304 (1%) | 3/305 (1%) | ||
| Basal cell carcinoma | 0/304 (0%) | 1/305 (0.3%) | ||
| Blast cell crisis | 5/304 (1.6%) | 1/305 (0.3%) | ||
| Leukaemia recurrent | 2/304 (0.7%) | 0/305 (0%) | ||
| Chronic myeloid leukaemia | 22/304 (7.2%) | 21/305 (6.9%) | ||
| Leukaemia | 1/304 (0.3%) | 3/305 (1%) | ||
| Leukaemic infiltration | 2/304 (0.7%) | 0/305 (0%) | ||
| Nervous system disorders | ||||
| Arachnoiditis | 0/304 (0%) | 1/305 (0.3%) | ||
| Central nervous system lesion | 2/304 (0.7%) | 0/305 (0%) | ||
| Coma | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Quadriparesis | 1/304 (0.3%) | 0/305 (0%) | ||
| Central nervous system haemorrhage | 5/304 (1.6%) | 3/305 (1%) | ||
| Dementia Alzheimer's type | 0/304 (0%) | 1/305 (0.3%) | ||
| Sciatica | 1/304 (0.3%) | 0/305 (0%) | ||
| Spinal cord compression | 0/304 (0%) | 1/305 (0.3%) | ||
| Convulsion | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Haemorrhagic stroke | 1/304 (0.3%) | 0/305 (0%) | ||
| Hydrocephalus | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Peripheral sensory neuropathy | 2/304 (0.7%) | 0/305 (0%) | ||
| Depressed level of consciousness | 1/304 (0.3%) | 0/305 (0%) | ||
| Speech disorder | 0/304 (0%) | 1/305 (0.3%) | ||
| Stupor | 0/304 (0%) | 1/305 (0.3%) | ||
| Subarachnoid haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Cerebral ischaemia | 1/304 (0.3%) | 0/305 (0%) | ||
| Headache | 3/304 (1%) | 8/305 (2.6%) | ||
| Transient ischaemic attack | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Cerebral haematoma | 1/304 (0.3%) | 0/305 (0%) | ||
| Cerebrovascular accident | 1/304 (0.3%) | 3/305 (1%) | ||
| Demyelinating polyneuropathy | 1/304 (0.3%) | 0/305 (0%) | ||
| Encephalomalacia | 0/304 (0%) | 1/305 (0.3%) | ||
| Haemorrhage intracranial | 3/304 (1%) | 1/305 (0.3%) | ||
| Benign intracranial hypertension | 0/304 (0%) | 1/305 (0.3%) | ||
| Cerebral haemorrhage | 1/304 (0.3%) | 3/305 (1%) | ||
| Encephalopathy | 1/304 (0.3%) | 0/305 (0%) | ||
| Extrapyramidal disorder | 1/304 (0.3%) | 0/305 (0%) | ||
| Grand mal convulsion | 1/304 (0.3%) | 0/305 (0%) | ||
| Monoplegia | 1/304 (0.3%) | 0/305 (0%) | ||
| Aphasia | 1/304 (0.3%) | 0/305 (0%) | ||
| Leukoencephalopathy | 0/304 (0%) | 1/305 (0.3%) | ||
| Motor dysfunction | 1/304 (0.3%) | 0/305 (0%) | ||
| Peripheral motor neuropathy | 1/304 (0.3%) | 0/305 (0%) | ||
| Syncope | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Psychiatric disorders | ||||
| Suicidal ideation | 0/304 (0%) | 1/305 (0.3%) | ||
| Anxiety | 0/304 (0%) | 1/305 (0.3%) | ||
| Confusional state | 2/304 (0.7%) | 2/305 (0.7%) | ||
| Panic attack | 0/304 (0%) | 1/305 (0.3%) | ||
| Renal and urinary disorders | ||||
| Urinary retention | 0/304 (0%) | 1/305 (0.3%) | ||
| Tubulointerstitial nephritis | 0/304 (0%) | 1/305 (0.3%) | ||
| Renal failure | 7/304 (2.3%) | 3/305 (1%) | ||
| Renal failure acute | 6/304 (2%) | 2/305 (0.7%) | ||
| Haematuria | 1/304 (0.3%) | 0/305 (0%) | ||
| Reproductive system and breast disorders | ||||
| Vaginal haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Benign prostatic hyperplasia | 0/304 (0%) | 1/305 (0.3%) | ||
| Pelvic pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Uterine haemorrhage | 1/304 (0.3%) | 0/305 (0%) | ||
| Ovarian cyst | 0/304 (0%) | 1/305 (0.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Lung infiltration | 7/304 (2.3%) | 5/305 (1.6%) | ||
| Organising pneumonia | 0/304 (0%) | 1/305 (0.3%) | ||
| Pneumonia aspiration | 0/304 (0%) | 1/305 (0.3%) | ||
| Pulmonary embolism | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Respiratory failure | 5/304 (1.6%) | 4/305 (1.3%) | ||
| Haemoptysis | 1/304 (0.3%) | 0/305 (0%) | ||
| Oropharyngeal pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Pulmonary alveolar haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Respiratory distress | 0/304 (0%) | 2/305 (0.7%) | ||
| Pleural effusion | 34/304 (11.2%) | 50/305 (16.4%) | ||
| Pneumothorax | 1/304 (0.3%) | 0/305 (0%) | ||
| Respiratory tract haemorrhage | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Acute respiratory distress syndrome | 2/304 (0.7%) | 0/305 (0%) | ||
| Acute respiratory failure | 0/304 (0%) | 1/305 (0.3%) | ||
| Dyspnoea | 9/304 (3%) | 15/305 (4.9%) | ||
| Interstitial lung disease | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Lung disorder | 2/304 (0.7%) | 1/305 (0.3%) | ||
| Pulmonary haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Pulmonary hypertension | 2/304 (0.7%) | 2/305 (0.7%) | ||
| Atelectasis | 1/304 (0.3%) | 0/305 (0%) | ||
| Epistaxis | 2/304 (0.7%) | 0/305 (0%) | ||
| Pneumonitis | 3/304 (1%) | 3/305 (1%) | ||
| Productive cough | 0/304 (0%) | 1/305 (0.3%) | ||
| Pulmonary oedema | 1/304 (0.3%) | 5/305 (1.6%) | ||
| Chylothorax | 0/304 (0%) | 1/305 (0.3%) | ||
| Cough | 1/304 (0.3%) | 3/305 (1%) | ||
| Haemothorax | 0/304 (0%) | 1/305 (0.3%) | ||
| Hypoxia | 3/304 (1%) | 4/305 (1.3%) | ||
| Pleuritic pain | 1/304 (0.3%) | 0/305 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Erythema | 1/304 (0.3%) | 0/305 (0%) | ||
| Purpura | 1/304 (0.3%) | 0/305 (0%) | ||
| Skin lesion | 0/304 (0%) | 1/305 (0.3%) | ||
| Palmar-plantar erythrodysaesthesia syndrome | 0/304 (0%) | 1/305 (0.3%) | ||
| Rash pruritic | 0/304 (0%) | 1/305 (0.3%) | ||
| Exfoliative rash | 0/304 (0%) | 1/305 (0.3%) | ||
| Necrotising panniculitis | 1/304 (0.3%) | 0/305 (0%) | ||
| Rash | 1/304 (0.3%) | 1/305 (0.3%) | ||
| Surgical and medical procedures | ||||
| Colostomy | 1/304 (0.3%) | 0/305 (0%) | ||
| Vascular disorders | ||||
| Arterial haemorrhage | 0/304 (0%) | 1/305 (0.3%) | ||
| Thrombosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Vasculitis | 2/304 (0.7%) | 0/305 (0%) | ||
| Hypertension | 0/304 (0%) | 3/305 (1%) | ||
| Ischaemia | 0/304 (0%) | 1/305 (0.3%) | ||
| Poor venous access | 0/304 (0%) | 1/305 (0.3%) | ||
| Deep vein thrombosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Hypotension | 4/304 (1.3%) | 3/305 (1%) | ||
| Circulatory collapse | 0/304 (0%) | 1/305 (0.3%) | ||
| Venous thrombosis | 0/304 (0%) | 1/305 (0.3%) | ||
| Haemorrhage | 1/304 (0.3%) | 0/305 (0%) | ||
| Labile blood pressure | 1/304 (0.3%) | 0/305 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Dasatinib 140 mg QD | Dasatinib 70 mg BID | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 289/304 (95.1%) | 290/305 (95.1%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile neutropenia | 7/304 (2.3%) | 16/305 (5.2%) | ||
| Neutropenia | 36/304 (11.8%) | 35/305 (11.5%) | ||
| Anaemia | 33/304 (10.9%) | 34/305 (11.1%) | ||
| Thrombocytopenia | 45/304 (14.8%) | 40/305 (13.1%) | ||
| Cardiac disorders | ||||
| Pericardial effusion | 4/304 (1.3%) | 19/305 (6.2%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 44/304 (14.5%) | 37/305 (12.1%) | ||
| Abdominal pain upper | 24/304 (7.9%) | 17/305 (5.6%) | ||
| Nausea | 103/304 (33.9%) | 91/305 (29.8%) | ||
| Vomiting | 81/304 (26.6%) | 81/305 (26.6%) | ||
| Abdominal pain | 37/304 (12.2%) | 39/305 (12.8%) | ||
| Gingival bleeding | 16/304 (5.3%) | 13/305 (4.3%) | ||
| Diarrhoea | 131/304 (43.1%) | 147/305 (48.2%) | ||
| Dyspepsia | 24/304 (7.9%) | 15/305 (4.9%) | ||
| Haemorrhoids | 16/304 (5.3%) | 16/305 (5.2%) | ||
| Stomatitis | 17/304 (5.6%) | 18/305 (5.9%) | ||
| General disorders | ||||
| Chills | 12/304 (3.9%) | 19/305 (6.2%) | ||
| Chest pain | 35/304 (11.5%) | 22/305 (7.2%) | ||
| Fatigue | 86/304 (28.3%) | 90/305 (29.5%) | ||
| Pain | 15/304 (4.9%) | 18/305 (5.9%) | ||
| Pyrexia | 112/304 (36.8%) | 99/305 (32.5%) | ||
| Oedema peripheral | 52/304 (17.1%) | 65/305 (21.3%) | ||
| Asthenia | 35/304 (11.5%) | 34/305 (11.1%) | ||
| Infections and infestations | ||||
| Oral herpes | 22/304 (7.2%) | 12/305 (3.9%) | ||
| Pneumonia | 17/304 (5.6%) | 17/305 (5.6%) | ||
| Nasopharyngitis | 21/304 (6.9%) | 18/305 (5.9%) | ||
| Upper respiratory tract infection | 31/304 (10.2%) | 29/305 (9.5%) | ||
| Urinary tract infection | 25/304 (8.2%) | 16/305 (5.2%) | ||
| Injury, poisoning and procedural complications | ||||
| Contusion | 18/304 (5.9%) | 8/305 (2.6%) | ||
| Investigations | ||||
| Weight decreased | 51/304 (16.8%) | 53/305 (17.4%) | ||
| Weight increased | 32/304 (10.5%) | 33/305 (10.8%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 51/304 (16.8%) | 65/305 (21.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 30/304 (9.9%) | 25/305 (8.2%) | ||
| Pain in extremity | 48/304 (15.8%) | 37/305 (12.1%) | ||
| Myalgia | 33/304 (10.9%) | 30/305 (9.8%) | ||
| Arthralgia | 57/304 (18.8%) | 45/305 (14.8%) | ||
| Back pain | 37/304 (12.2%) | 34/305 (11.1%) | ||
| Musculoskeletal pain | 15/304 (4.9%) | 20/305 (6.6%) | ||
| Nervous system disorders | ||||
| Dizziness | 26/304 (8.6%) | 26/305 (8.5%) | ||
| Headache | 112/304 (36.8%) | 100/305 (32.8%) | ||
| Psychiatric disorders | ||||
| Anxiety | 19/304 (6.3%) | 18/305 (5.9%) | ||
| Depression | 19/304 (6.3%) | 22/305 (7.2%) | ||
| Insomnia | 19/304 (6.3%) | 22/305 (7.2%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Oropharyngeal pain | 33/304 (10.9%) | 16/305 (5.2%) | ||
| Pleural effusion | 72/304 (23.7%) | 106/305 (34.8%) | ||
| Dyspnoea | 79/304 (26%) | 88/305 (28.9%) | ||
| Epistaxis | 31/304 (10.2%) | 22/305 (7.2%) | ||
| Cough | 84/304 (27.6%) | 93/305 (30.5%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Pruritus | 29/304 (9.5%) | 25/305 (8.2%) | ||
| Alopecia | 8/304 (2.6%) | 21/305 (6.9%) | ||
| Night sweats | 19/304 (6.3%) | 15/305 (4.9%) | ||
| Dry skin | 17/304 (5.6%) | 11/305 (3.6%) | ||
| Petechiae | 26/304 (8.6%) | 21/305 (6.9%) | ||
| Rash | 58/304 (19.1%) | 65/305 (21.3%) | ||
| Vascular disorders | ||||
| Hypertension | 24/304 (7.9%) | 22/305 (7.2%) | ||
| Haematoma | 11/304 (3.6%) | 19/305 (6.2%) | ||
Limitations/Caveats
Amendment 3 (7 March 2007) allowed participants to switch from BID to QD dosing. Therefore, results for BID summarized by treatment group after Year 2 may not be a complete reflection of the BID experience and should be interpreted with this in mind.
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:
NCT00123487
Other Study ID Numbers:
- CA180-035
- NCT00331396
First Posted:
Jul 25, 2005
Last Update Posted:
Nov 2, 2014
Last Verified:
Oct 1, 2014