Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00103844
• Collaborator: (none)
• Enrollment: 150
• Locations: 131
• Arms: 2
• Duration (Months): 36.9
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary purpose of this study is to estimate the major cytogenetic response rates of BMS-354825 and imatinib (800 mg/d) in subjects with chronic phase, Philadelphia chromosome positive, chronic myeloid leukemia (PH+ CML) with disease resistant to imatinib at a dose of 400-600 mg/d.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukemia; Philadelphia-Positive Myeloid Leukemia	Drug: Dasatinib; Drug: Imatinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Multi-Center Open Label Study of BMS-354825 vs. Imatinib Mesylate (Gleevec) 800 mg/d in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to Imatinib at a Dose at 400 - 600 mg/d
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Aug 1, 2006
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Active Comparator	Drug: Dasatinib; Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks; Other Names: Sprycel BMS-354825
Experimental: 2 Active Comparator	Drug: Imatinib; Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Major Cytogenetic Response (MCyR) at Week 12 [Week 12]

   Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; >0% to 35% Ph+ cells in metaphase in bone marrow).

Secondary Outcome Measures

1. MCyR at Any Time Prior to Crossover [Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.]

   Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (>0% to 35% Ph+ cells in metaphase in bone marrow).

2. Duration of MCyR at 12 Months and 18 Months [12 months, 18 months]

   Percentage of participants who achieved MCyR and did not progress at 12 and 18 months.

3. Duration of MCyR at 24 Months [24 Months]

   Percentage of participants who achieved MCyR and did not progress at 24 months.

4. Time to MCyR Prior to Crossover [Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.]

   Median time from first dosing date to date of MCyR

5. Complete Hematologic Response (CHR) at Any Time Prior to Crossover [Baseline (within 4 weeks of Day 1), weekly until Week 12 and then every 12 weeks until crossover or off-study; restricted to precrossover measurements.]

   Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

6. Duration of Complete Hematologic Response (CHR) [12 months, 24 months]

   Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

7. Time to CHR Prior to Crossover [Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.]

   Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

8. Major Molecular Response (MMR) [Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.]

   Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), 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.

9. CHR After Crossover [Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.]

   Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.

10. Cytogenetic Response After Crossover [every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements]

    Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (>0% to 35% Ph+ cells in metaphase in bone marrow).

11. Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover [Continuously from baseline through 2 years]

    AE=any new untoward medical occurrence or worsening of a pre-existing 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)

12. Health-Related Quality of Life Prior to Crossover [Every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment. Last questionnaire was to be completed at first follow-up visit after off-study date.]

    Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). 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, & SWB score change of 2 or more=minimal clinical important change.

13. Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib [Day 8: pretreatment trough sample, a sample between 30 minutes and 3 hours following treatment, a sample between 5 and 8 hours following treatment, and a sample at 12 hours, prior to the next dose.]

    Number of participants from which blood samples were collected for population PK studies.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Men and women, 18 years of age or older.

• Subjects with Chronic Phase Ph+ CML.

• Subjects have not been treated with imatinib at a dose >600 mg/day.

• Subjects developed resistance to disease while receiving an imatinib dose 400-600 mg/day.

• Able to tolerate imatinib at the highest dose the subject had received in the past.

• Demonstrate adequate renal and hepatic function.

• Women of childbearing potential must have a negative serum or urine pregnancy test, must be using an adequate method of contraception.

Exclusion Criteria:

• Women who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period for a least 1 month before and at least 3 months after the completion of the study.

• Women using a prohibited contraceptive method.

• Women 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.

• Prior treatment with imatinib at a dose >600 mg/day.

• Subjects who have previously identified specific BCR-ABL mutations.

• Previous diagnosis of accelerated phase or blast crisis CML.

• Intolerance to imatinib at any dose.

• Subjects who are eligible and willing to undergo transplantation during the screening period.

• Serious uncontrolled medical disorder or active infection.

• Uncontrolled or significant cardiovascular disease.

• Uncontrolled hypertension.

• Dementia or altered mental status.

• Evidence of organ dysfunction.

• 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.

• Subjects taking certain medications that are accepted to have a risk of causing Torsades de Pointes.

• Subjects taking medications that irreversibly inhibit platelet function or anticoagulants.

• Prior therapy with BMS-354825.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Birmingham	Alabama	United States
2	Local Institution	Anaheim	California	United States
3	Local Institution	Bakersfield	California	United States
4	Local Institution	Fullerton	California	United States
5	Local Institution	Loma Linda	California	United States
6	Local Institution	Los Angeles	California	United States
7	Local Institution	Monterey Park	California	United States
8	Local Institution	San Diego	California	United States
9	Local Institution	Santa Barbara	California	United States
10	Local Institution	Santa Maria	California	United States
11	Local Institution	Stanford	California	United States
12	Local Institution	Vallejo	California	United States
13	Local Institution	Aurora	Colorado	United States
14	Local Institution	Hartford	Connecticut	United States
15	Local Institution	Washington	District of Columbia	United States
16	Local Institution	Jacksonville	Florida	United States
17	Local Institution	Tampa	Florida	United States
18	Local Institution	Athens	Georgia	United States
19	Local Institution	Atlanta	Georgia	United States
20	Local Institution	Lawrenceville	Georgia	United States
21	Local Institution	Tucker	Georgia	United States
22	Local Institution	Chicago	Illinois	United States
23	Local Institution	Peoria	Illinois	United States
24	Local Institution	Indianapolis	Indiana	United States
25	Local Institution	Kansas City	Kansas	United States
26	Local Institution	Lexington	Kentucky	United States
27	Local Institution	Boston	Massachusetts	United States
28	Local Institution	Minneapolis	Minnesota	United States
29	Local Institution	Rochester	Minnesota	United States
30	Local Institution	Columbia	Missouri	United States
31	Local Institution	Kansas City	Missouri	United States
32	Local Institution	St. Louis	Missouri	United States
33	Local Institution	Omaha	Nebraska	United States
34	Local Institution	Hackensack	New Jersey	United States
35	Local Institution	Morristown	New Jersey	United States
36	Local Institution	New Brunswick	New Jersey	United States
37	Local Institution	Cary	North Carolina	United States
38	Local Institution	Chapel Hill	North Carolina	United States
39	Local Institution	Oklahoma City	Oklahoma	United States
40	Local Institution	Tulsa	Oklahoma	United States
41	Local Institution	Portland	Oregon	United States
42	Local Institution	Pittsburgh	Pennsylvania	United States
43	Local Institution	Greenville	South Carolina	United States
44	Local Institution	Nashville	Tennessee	United States
45	Local Institution	Dallas	Texas	United States
46	Local Institution	Fort Worth	Texas	United States
47	Local Institution	Houston	Texas	United States
48	Local Institution	San Antonio	Texas	United States
49	Local Institution	Tyler	Texas	United States
50	Local Institution	Norfolk	Virginia	United States
51	Local Institution	Seattle	Washington	United States
52	Local Institution	Spokane	Washington	United States
53	Local Institution	Vancouver	Washington	United States
54	Local Institution	Buenos Aires		Argentina
55	Local Institution	Cordoba		Argentina
56	Local Institution	Camperdown	New South Wales	Australia
57	Local Institution	St. Leonards	New South Wales	Australia
58	Local Institution	South Brisbane	Queensland	Australia
59	Local Institution	Adelaide	South Australia	Australia
60	Local Institution	Perth	Western Australia	Australia
61	Local Institution	Wein		Austria
62	Local Institution	B-Leuven		Belgium
63	Local Institution	Brugge		Belgium
64	Local Institution	Bruxelles		Belgium
65	Local Institution	Charleroi		Belgium
66	Local Institution	Edegem		Belgium
67	Local Institution	Yvoir		Belgium
68	Local Institution	Curitiba	Parana	Brazil
69	Local Institution	Rio De Janeiro		Brazil
70	Local Institution	Sao Paulo		Brazil
71	Local Institution	Edmonton	Alberta	Canada
72	Local Institution	Vancouver	British Columbia	Canada
73	Local Institution	Toronto	Ontario	Canada
74	Local Institution	Montreal	Quebec	Canada
75	Local Institution	Beijing		China
76	Local Institution	Shanghai		China
77	Local Institution	Aarhus		Denmark
78	Local Institution	Tallin		Estonia
79	Local Institution	Helsinki		Finland
80	Local Institution	Lille		France
81	Local Institution	Lyon Cedex 03		France
82	Local Institution	Nantes		France
83	Local Institution	Paris		France
84	Local Institution	Pessac		France
85	Local Institution	Poitiers		France
86	Local Institution	Strasbourg Cedex		France
87	Local Institution	Dresden		Germany
88	Local Institution	Groenkloof		Germany
89	Local Institution	Hamburg		Germany
90	Local Institution	Leipzig		Germany
91	Local Institution	Mainz		Germany
92	Local Institution	Mannheim		Germany
93	Local Institution	Budapest		Hungary
94	Local Institution	Dublin		Ireland
95	Local Institution	Ramat-Gan		Israel
96	Local Institution	Bari		Italy
97	Local Institution	Bologna		Italy
98	Local Institution	Milano		Italy
99	Local Institution	Napoli		Italy
100	Local Institution	Orbassano		Italy
101	Local Institution	Roma		Italy
102	Local Institution	Kyunggi-Do		Korea, Republic of
103	Local Institution	Trondheim		Norway
104	Local Institution	Lima		Peru
105	Local Institution	Quezon City		Philippines
106	Local Institution	Katowice		Poland
107	Local Institution	Krakow		Poland
108	Local Institution	Lublin		Poland
109	Local Institution	Warsaw		Poland
110	Local Institution	San Juan		Puerto Rico
111	Local Institution	Moscow		Russian Federation
112	Local Institution	St. Petersburg		Russian Federation
113	Local Institution	Singapore		Singapore
114	Local Institution	Bloemfontein	Free State	South Africa
115	Local Institution	Parktown	Gauteng	South Africa
116	Local Institution	Soweto	Gauteng	South Africa
117	Local Institution	Barcelona		Spain
118	Local Institution	Madrid		Spain
119	Local Institution	Gothenburg		Sweden
120	Local Institution	Lund		Sweden
121	Local Institution	Stockholm		Sweden
122	Local Institution	Umea		Sweden
123	Local Institution	Uppsala		Sweden
124	Local Institution	Basel		Switzerland
125	Local Institution	Bellinzona		Switzerland
126	Local Institution	Taipei		Taiwan
127	Local Institution	Taoyuan		Taiwan
128	Local Institution	Bangkok		Thailand
129	Local Institution	Glasglow	Central	United Kingdom
130	Local Institution	London	Greater London	United Kingdom
131	Local Institution	Newcastle	Tyne and Wear	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

• Kantarjian H, Pasquini R, Lévy V, Jootar S, Holowiecki J, Hamerschlak N, Hughes T, Bleickardt E, Dejardin D, Cortes J, Shah NP. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R). Cancer. 2009 Sep 15;115(18):4136-47. doi: 10.1002/cncr.24504.
• 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.

• ClinicalTrials.gov Identifier: NCT00103844
• Other Study ID Numbers: CA180-017
• First Posted: Feb 16, 2005
• Last Update Posted: Aug 10, 2010
• Last Verified: Jun 1, 2010

• Keywords provided by , ,: Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome; Imatinib Mesylate; Dasatinib

Study Results

Participant Flow

Pre-assignment Detail	166 subjects enrolled; 16 failed screening and were not treated (2 subjects were double-randomizations, 13 subjects failed inclusion criteria, 1 subject withdrew consent during screening.)

Arm/Group Title	Dasatinib First	Imatinib First
Arm/Group Description	Dasatinib 70 mg twice a day (BID) in the first intervention period and, if intolerance to dasatinib or progression, imatinib 400 mg BID in the second intervention period (after washout period).	Imatinib 400 mg BID in the first intervention period and, if intolerance to imatinib or progression or lack of efficacy, dasatinib 70 mg BID in the second intervention period (after washout period).
Period Title: Overall Study
STARTED	101	49
Crossed Over	22	40
COMPLETED	101	49
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Dasatinib	Imatinib	Total
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID	Total of all reporting groups
Overall Participants	101	49	150
Age, Customized (participants) [Number]
Between 21 and 45 years	36 35.6%	15 30.6%	51 34%
Between 46 and 65 years	48 47.5%	28 57.1%	76 50.7%
Between 66 and 75 years	13 12.9%	5 10.2%	18 12%
>75 years	4 4%	1 2%	5 3.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51 (13.6)	50 (13.6)	51 (13.6)
Sex: Female, Male (Count of Participants)
Female	48 47.5%	27 55.1%	75 50%
Male	53 52.5%	22 44.9%	75 50%
Race/Ethnicity, Customized (Number) [Number]
Asian	6 5.9%	3 6.1%	9 6%
Black or African American	2 2%	1 2%	3 2%
White	87 86.1%	43 87.8%	130 86.7%
Other	6 5.9%	2 4.1%	8 5.3%
Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS) (Number) [Number]
Score=0 (fully active)	71 70.3%	34 69.4%	105 70%
Score=1 (ambulatory, light/sedentary work)	27 26.7%	12 24.5%	39 26%
Score=2 (ambulatory, all selfcare, unable to work)	0 0%	0 0%	0 0%
Score=3 (limited selfcare, some bed confinement)	0 0%	0 0%	0 0%
Score=4 (completely disabled)	0 0%	0 0%	0 0%
Score=5 (dead)	0 0%	0 0%	0 0%
Not Reported	3 3%	3 6.1%	6 4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Major Cytogenetic Response (MCyR) at Week 12
Description	Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; >0% to 35% Ph+ cells in metaphase in bone marrow).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized subjects

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	49
Number [Participants]	36 35.6%	14 28.6%

2. Secondary Outcome

Title	MCyR at Any Time Prior to Crossover
Description	Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as CCyR (0% Ph+ cells in metaphase in bone marrow) or PCyR (>0% to 35% Ph+ cells in metaphase in bone marrow).
Time Frame	Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	49
MCyR (CCyR + PCyR)	54 53.5%	16 32.7%
CCyR (0% Ph+ cells)	44 43.6%	9 18.4%
PCyR (>0% to 35% Ph+ cells)	10 9.9%	7 14.3%

3. Secondary Outcome

Title	Duration of MCyR at 12 Months and 18 Months
Description	Percentage of participants who achieved MCyR and did not progress at 12 and 18 months.
Time Frame	12 months, 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	49
12 months	92 91.1%	74 151%
18 months	90 89.1%	74 151%

4. Secondary Outcome

Title	Duration of MCyR at 24 Months
Description	Percentage of participants who achieved MCyR and did not progress at 24 months.
Time Frame	24 Months

Outcome Measure Data

Analysis Population Description

In the imatinib group, the 24 months timepoint was beyond the maximum observed time.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	0
Number [Percentage of Participants]	90 89.1%

5. Secondary Outcome

Title	Time to MCyR Prior to Crossover
Description	Median time from first dosing date to date of MCyR
Time Frame	Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.

Outcome Measure Data

Analysis Population Description

Population consists of the number of responders in each treatment group

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	54	16
Median (Full Range) [months]	2.8	2.8

6. Secondary Outcome

Title	Complete Hematologic Response (CHR) at Any Time Prior to Crossover
Description	Participants achieving CHR prior to crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time Frame	Baseline (within 4 weeks of Day 1), weekly until Week 12 and then every 12 weeks until crossover or off-study; restricted to precrossover measurements.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	49
Number [Participants]	94 93.1%	40 81.6%

7. Secondary Outcome

Title	Duration of Complete Hematologic Response (CHR)
Description	Percentage of participants who achieved CHR and did not progress at specified time points. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time Frame	12 months, 24 months

Outcome Measure Data

Analysis Population Description

Number of participants achieving CHR in each treatment group

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	94	40
12 months	92 91.1%	82 167.3%
24 months	84 83.2%	73 149%

8. Secondary Outcome

Title	Time to CHR Prior to Crossover
Description	Median time from first dosing date to date of CHR. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time Frame	Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.

Outcome Measure Data

Analysis Population Description

Number of participants achieving CHR in each treatment group

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	94	40
Median (Full Range) [weeks]	2.1	2.1

9. Secondary Outcome

Title	Major Molecular Response (MMR)
Description	Number of participants Achieving MMR. MMR is defined as ≤3 log reduction (ie, international ratio ≤0.1), 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	Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.

Outcome Measure Data

Analysis Population Description

Participants assessed for MMR only

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	99	45
Number [participants]	29 28.7%	6 12.2%

10. Secondary Outcome

Title	CHR After Crossover
Description	Participants achieving CHR after crossover. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets < 450,000/mm³; no blasts or promyelocytes in peripheral blood; < 5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤ 20%; no extramedullary involvement. Confirmed CHR is defined as CHR maintained at least 4 weeks after first documented at ≥ Day 14. Failure to maintain criteria of CHR was defined by 2 or more consecutive records of non-response.
Time Frame	Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.

Outcome Measure Data

Analysis Population Description

Participants evaluable for response after crossover

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	39	20
Number [Participants]	37 36.6%	13 26.5%

11. Secondary Outcome

Title	Cytogenetic Response After Crossover
Description	Cytogenetic response was based on the prevalence of Ph+ metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (0% Ph+ cells in metaphase in bone marrow) or Partial CyR (>0% to 35% Ph+ cells in metaphase in bone marrow).
Time Frame	every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements

Outcome Measure Data

Analysis Population Description

Participants evaluable for after crossover response

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	39	20
Major Cytogenetic Response (MCyR)	19 18.8%	3 6.1%
Complete Cytogenetic Response (CCyR)	15 14.9%	0 0%
Partial Cytogenetic Response (PCyR)	4 4%	3 6.1%

12. Secondary Outcome

Title	Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover
Description	AE=any new untoward medical occurrence or worsening of a pre-existing 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 treated participants

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	101	49
Any Adverse Event (AE)	100 99%	45 91.8%
Grade 3-4 AEs	67 66.3%	21 42.9%
Drug-related AEs	94 93.1%	44 89.8%
Drug-related Grade 3-4 AEs	62 61.4%	19 38.8%
Death within 30 days of last dose	1 1%	0 0%
Drug-related Serious AEs	28 27.7%	3 6.1%
AEs leading to discontinuation	23 22.8%	10 20.4%
Fluid Retention AEs - Overall	39 38.6%	21 42.9%
Fluid Retention AEs - Superficial Edema	20 19.8%	21 42.9%
Fluid Retention AEs - Pleural Effusion	25 24.8%	0 0%
Fluid Retention AEs - Other	9 8.9%	0 0%
Grade 3-4 Hematologic Toxicity - Anemia	20 19.8%	4 8.2%
Grade 3-4 Hematologic Toxicity - Thrombocytopenia	58 57.4%	7 14.3%
Grade 3-4 Hematologic Toxicity - Neutropenia	64 63.4%	19 38.8%
Grade 3-4 Hematologic Toxicity - Leukopenia	24 23.8%	8 16.3%

13. Secondary Outcome

Title	Health-Related Quality of Life Prior to Crossover
Description	Health-related quality of life as measured by Functional Assessment of Cancer Therapy-General (FACT-G). FACT-G=27 questions in 4 domains: physical, social/family, emotional, & functional well-being (PWB, SWB, EWB, FWB). 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, & SWB score change of 2 or more=minimal clinical important change.
Time Frame	Every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment. Last questionnaire was to be completed at first follow-up visit after off-study date.

Outcome Measure Data

Analysis Population Description

Since single-arm quality-of-life data are not interpretable in a non-comparative trial, these data were not analyzed.

Arm/Group Title	Dasatinib	Imatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)	Imatinib 400 mg BID
Measure Participants	0	0

14. Secondary Outcome

Title	Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Description	Number of participants from which blood samples were collected for population PK studies.
Time Frame	Day 8: pretreatment trough sample, a sample between 30 minutes and 3 hours following treatment, a sample between 5 and 8 hours following treatment, and a sample at 12 hours, prior to the next dose.

Outcome Measure Data

Analysis Population Description

Blood samples that were to contribute to PK modeling were collected from 78 participants,to be included in separate population PK analyses. Although blood sample collection was listed as a secondary endpoint, no study-specific PK analyses were planned for this report.

Arm/Group Title	Dasatinib
Arm/Group Description	Dasatinib 70 mg twice a day (BID)
Measure Participants	78
Number [participants]	78 77.2%

Adverse Events

Arm/Group Title	DASATINIB		IMATINIB
Arm/Group Description	Dasatinib 70 mg twice a day (BID)		Imatinib 400 mg BID
All Cause Mortality
	DASATINIB		IMATINIB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	DASATINIB		IMATINIB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	43/101 (42.6%)		4/49 (8.2%)
Blood and lymphatic system disorders
ANAEMIA	3/101 (3%)		0/49 (0%)
THROMBOCYTOPENIA	6/101 (5.9%)		0/49 (0%)
FEBRILE NEUTROPENIA	0/101 (0%)		1/49 (2%)
Cardiac disorders
ATRIAL FIBRILLATION	3/101 (3%)		0/49 (0%)
PERICARDIAL EFFUSION	1/101 (1%)		0/49 (0%)
VENTRICULAR ARRHYTHMIA	1/101 (1%)		0/49 (0%)
RIGHT VENTRICULAR DYSFUNCTION	1/101 (1%)		0/49 (0%)
Eye disorders
CATARACT	1/101 (1%)		0/49 (0%)
RETINAL DETACHMENT	0/101 (0%)		1/49 (2%)
Gastrointestinal disorders
DIARRHOEA	1/101 (1%)		0/49 (0%)
GASTRITIS	1/101 (1%)		0/49 (0%)
ABDOMINAL PAIN	0/101 (0%)		1/49 (2%)
ANAL HAEMORRHAGE	1/101 (1%)		0/49 (0%)
ANORECTAL DISORDER	1/101 (1%)		0/49 (0%)
INTESTINAL OBSTRUCTION	1/101 (1%)		0/49 (0%)
GASTROINTESTINAL HAEMORRHAGE	2/101 (2%)		0/49 (0%)
General disorders
DEATH	1/101 (1%)		0/49 (0%)
PYREXIA	5/101 (5%)		0/49 (0%)
CHEST DISCOMFORT	1/101 (1%)		0/49 (0%)
MULTI-ORGAN FAILURE	1/101 (1%)		0/49 (0%)
Hepatobiliary disorders
CHOLECYSTITIS	1/101 (1%)		0/49 (0%)
HEPATIC LESION	1/101 (1%)		0/49 (0%)
Infections and infestations
MUMPS	1/101 (1%)		0/49 (0%)
SEPSIS	1/101 (1%)		0/49 (0%)
INFECTION	2/101 (2%)		0/49 (0%)
PNEUMONIA	7/101 (6.9%)		0/49 (0%)
CELLULITIS	1/101 (1%)		0/49 (0%)
APPENDICITIS	1/101 (1%)		0/49 (0%)
BRONCHOPNEUMONIA	1/101 (1%)		0/49 (0%)
PNEUMONIA STREPTOCOCCAL	1/101 (1%)		0/49 (0%)
GASTROINTESTINAL INFECTION	1/101 (1%)		0/49 (0%)
RESPIRATORY TRACT INFECTION	1/101 (1%)		0/49 (0%)
Injury, poisoning and procedural complications
CONTUSION	1/101 (1%)		0/49 (0%)
TRANSFUSION REACTION	1/101 (1%)		0/49 (0%)
Investigations
BLOOD CREATININE INCREASED	1/101 (1%)		0/49 (0%)
Metabolism and nutrition disorders
DEHYDRATION	2/101 (2%)		0/49 (0%)
Musculoskeletal and connective tissue disorders
OSTEONECROSIS	1/101 (1%)		1/49 (2%)
JOINT EFFUSION	0/101 (0%)		1/49 (2%)
OSTEOARTHRITIS	1/101 (1%)		0/49 (0%)
OSTEOCHONDROSIS	0/101 (0%)		1/49 (2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ANAL CANCER STAGE 0	1/101 (1%)		0/49 (0%)
BLAST CRISIS IN MYELOGENOUS LEUKAEMIA	1/101 (1%)		0/49 (0%)
Nervous system disorders
HEADACHE	0/101 (0%)		1/49 (2%)
Renal and urinary disorders
RENAL FAILURE	1/101 (1%)		0/49 (0%)
Reproductive system and breast disorders
CERVICAL DYSPLASIA	1/101 (1%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA	5/101 (5%)		0/49 (0%)
BRONCHOSPASM	1/101 (1%)		0/49 (0%)
PLEURAL EFFUSION	10/101 (9.9%)		0/49 (0%)
PULMONARY OEDEMA	1/101 (1%)		0/49 (0%)
LUNG INFILTRATION	1/101 (1%)		0/49 (0%)
PULMONARY EMBOLISM	2/101 (2%)		0/49 (0%)
RESPIRATORY DISORDER	1/101 (1%)		0/49 (0%)
PULMONARY HYPERTENSION	1/101 (1%)		0/49 (0%)
Surgical and medical procedures
KNEE ARTHROPLASTY	1/101 (1%)		0/49 (0%)
UTERINE DILATION AND CURETTAGE	1/101 (1%)		0/49 (0%)
Vascular disorders
HYPERTENSION	1/101 (1%)		0/49 (0%)
Other (Not Including Serious) Adverse Events
	DASATINIB		IMATINIB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	99/101 (98%)		43/49 (87.8%)
Blood and lymphatic system disorders
ANAEMIA	8/101 (7.9%)		4/49 (8.2%)
LEUKOPENIA	2/101 (2%)		3/49 (6.1%)
NEUTROPENIA	22/101 (21.8%)		8/49 (16.3%)
THROMBOCYTOPENIA	22/101 (21.8%)		5/49 (10.2%)
Eye disorders
EYE OEDEMA	1/101 (1%)		3/49 (6.1%)
EYELID OEDEMA	3/101 (3%)		4/49 (8.2%)
CONJUNCTIVITIS	6/101 (5.9%)		2/49 (4.1%)
CONJUNCTIVAL HAEMORRHAGE	6/101 (5.9%)		0/49 (0%)
Gastrointestinal disorders
NAUSEA	32/101 (31.7%)		19/49 (38.8%)
VOMITING	18/101 (17.8%)		13/49 (26.5%)
DIARRHOEA	48/101 (47.5%)		14/49 (28.6%)
DYSPEPSIA	12/101 (11.9%)		4/49 (8.2%)
GASTRITIS	9/101 (8.9%)		1/49 (2%)
TOOTHACHE	9/101 (8.9%)		1/49 (2%)
STOMATITIS	6/101 (5.9%)		2/49 (4.1%)
CONSTIPATION	9/101 (8.9%)		1/49 (2%)
ABDOMINAL PAIN	16/101 (15.8%)		5/49 (10.2%)
ABDOMINAL DISTENSION	7/101 (6.9%)		0/49 (0%)
ABDOMINAL PAIN UPPER	15/101 (14.9%)		0/49 (0%)
General disorders
PAIN	5/101 (5%)		3/49 (6.1%)
CHILLS	6/101 (5.9%)		4/49 (8.2%)
FATIGUE	46/101 (45.5%)		12/49 (24.5%)
PYREXIA	32/101 (31.7%)		8/49 (16.3%)
ASTHENIA	19/101 (18.8%)		3/49 (6.1%)
CHEST PAIN	8/101 (7.9%)		0/49 (0%)
FACE OEDEMA	6/101 (5.9%)		7/49 (14.3%)
FEELING COLD	3/101 (3%)		3/49 (6.1%)
OEDEMA PERIPHERAL	18/101 (17.8%)		10/49 (20.4%)
INFLUENZA LIKE ILLNESS	10/101 (9.9%)		2/49 (4.1%)
Infections and infestations
RHINITIS	9/101 (8.9%)		0/49 (0%)
PNEUMONIA	7/101 (6.9%)		0/49 (0%)
SINUSITIS	7/101 (6.9%)		1/49 (2%)
BRONCHITIS	10/101 (9.9%)		2/49 (4.1%)
ORAL HERPES	8/101 (7.9%)		2/49 (4.1%)
PHARYNGITIS	9/101 (8.9%)		1/49 (2%)
GASTROENTERITIS	8/101 (7.9%)		0/49 (0%)
NASOPHARYNGITIS	12/101 (11.9%)		2/49 (4.1%)
URINARY TRACT INFECTION	6/101 (5.9%)		1/49 (2%)
UPPER RESPIRATORY TRACT INFECTION	18/101 (17.8%)		7/49 (14.3%)
Injury, poisoning and procedural complications
CONTUSION	7/101 (6.9%)		1/49 (2%)
Investigations
WEIGHT DECREASED	27/101 (26.7%)		4/49 (8.2%)
WEIGHT INCREASED	14/101 (13.9%)		8/49 (16.3%)
Metabolism and nutrition disorders
ANOREXIA	23/101 (22.8%)		4/49 (8.2%)
HYPOPHOSPHATAEMIA	0/101 (0%)		3/49 (6.1%)
Musculoskeletal and connective tissue disorders
MYALGIA	13/101 (12.9%)		5/49 (10.2%)
BACK PAIN	16/101 (15.8%)		1/49 (2%)
BONE PAIN	13/101 (12.9%)		3/49 (6.1%)
ARTHRALGIA	17/101 (16.8%)		8/49 (16.3%)
MUSCLE SPASMS	4/101 (4%)		8/49 (16.3%)
PAIN IN EXTREMITY	20/101 (19.8%)		6/49 (12.2%)
MUSCULOSKELETAL PAIN	12/101 (11.9%)		1/49 (2%)
Nervous system disorders
HEADACHE	46/101 (45.5%)		6/49 (12.2%)
DIZZINESS	18/101 (17.8%)		3/49 (6.1%)
Psychiatric disorders
INSOMNIA	9/101 (8.9%)		3/49 (6.1%)
Reproductive system and breast disorders
BREAST PAIN	7/101 (6.9%)		0/49 (0%)
Respiratory, thoracic and mediastinal disorders
COUGH	29/101 (28.7%)		4/49 (8.2%)
DYSPNOEA	25/101 (24.8%)		2/49 (4.1%)
EPISTAXIS	1/101 (1%)		3/49 (6.1%)
PLEURAL EFFUSION	22/101 (21.8%)		0/49 (0%)
PHARYNGOLARYNGEAL PAIN	12/101 (11.9%)		2/49 (4.1%)
Skin and subcutaneous tissue disorders
RASH	30/101 (29.7%)		9/49 (18.4%)
ALOPECIA	11/101 (10.9%)		1/49 (2%)
PRURITUS	12/101 (11.9%)		1/49 (2%)
PETECHIAE	6/101 (5.9%)		2/49 (4.1%)
ECCHYMOSIS	2/101 (2%)		3/49 (6.1%)
PERIORBITAL OEDEMA	3/101 (3%)		4/49 (8.2%)
Vascular disorders
HYPERTENSION	9/101 (8.9%)		0/49 (0%)

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.