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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00123474




Registration number
NCT00123474
Ethics application status
Date submitted
21/07/2005
Date registered
25/07/2005
Date last updated
25/08/2016

Titles & IDs
Public title
Chronic Myelogenous Leukemia (CML) - Follow on: Study of BMS-354825 in Subjects With CML
Scientific title
A Randomized Two-by-Two, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 50 mg or 70 mg Twice Daily or 100 mg or 140 mg Once Daily in Subjects With Chronic Phase Philadelphia Chromosome or BCR-ABL Positive Chronic Myelogenous Leukemia Who Are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
Secondary ID [1] 0 0
CA180-034
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myeloid Leukemia, Chronic, Chronic-Phase 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - dasatinib
Treatment: Drugs - dasatinib
Treatment: Drugs - dasatinib
Treatment: Drugs - dasatinib

Experimental: 1 -

Experimental: 2 -

Experimental: 3 -

Experimental: 4 -


Treatment: Drugs: dasatinib
Tablets, Oral, 50 mg BID, indefinitely, survival study

Treatment: Drugs: dasatinib
Tablets, Oral, 70 mg BID, indefinitely, survival study

Treatment: Drugs: dasatinib
Tablets, Oral, 100 mg QD, indefinitely, survival study

Treatment: Drugs: dasatinib
Tablets, Oral, 140 mg QD, indefinitely, survival study
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent of Participants With Major Cytogenetic Response (MCyR) at 6 Months Follow-Up
Timepoint [1] 0 0
6 months
Secondary outcome [1] 0 0
Percent of Participants With MCyR At or Prior to 24 Months Follow-Up
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Percent of Participants With Complete Hematologic Response (CHR) at 6 and 24 Months Follow-Up
Timepoint [2] 0 0
6 months, 24 months
Secondary outcome [3] 0 0
Time to MCyR in Participants With MCyR at 6 Months Follow-Up
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Time to CHR in Participants With CHR at 6 Months Follow-Up
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Time to MCyR in Participants With MCyR at 24 Months Follow-Up
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Time to CHR in Participants With CHR At 24 Months Follow-Up
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Number of Participants With MCyR Whose Disease Progressed by 24 Months
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Number of Participants With CHR Whose Disease Progressed by 24 Months
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Number of Participants With MCyR and Baseline BCR-ABL Gene Mutation - All Treated Participants
Timepoint [9] 0 0
Baseline up to 24 months
Secondary outcome [10] 0 0
Percent of Imatinib-Resistant Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
Timepoint [10] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [11] 0 0
Percent of Imatinib-Resistant Participants With Overall Survival (OS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up
Timepoint [11] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [12] 0 0
Percent of Participants Intolerant to Imatinib With MCyR at 6 Months and at 24 Months Follow-Up, by QD and BID Schedules and by Total Daily Dose
Timepoint [12] 0 0
6 months, 24 months
Secondary outcome [13] 0 0
Percent of Participants Intolerant to Imatinib With CHR at 6 Months and at 24 Months Follow-Up
Timepoint [13] 0 0
6 months, 24 months
Secondary outcome [14] 0 0
Percent of Imatinib Intolerant Participants With Progression Free Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-Up
Timepoint [14] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [15] 0 0
Percent of Imatinib Intolerant Participants With Overall Survival After 24, 36, 48, 60, 72, and 84 Months of Follow-up
Timepoint [15] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [16] 0 0
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 6 Months Follow-Up
Timepoint [16] 0 0
6 months
Secondary outcome [17] 0 0
Percent of All Randomized Participants With Cytogenic and Hematologic Response by Dosing Schedule (QD or BID) and by Total Daily Dose (100 mg or 140 mg) at 24 Months Follow-Up
Timepoint [17] 0 0
24 months
Secondary outcome [18] 0 0
Percent of Participants With Progression Free Survival (PFS) at 24, 36, 48, 60, 72, and 84 Months Follow-Up by Dose Schedule and Total Daily Dose - All Randomized Participants
Timepoint [18] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [19] 0 0
Percent of Participants Overall Survival at 24, 36, 48, 60, 72, and 84 Months Follow-Up - All Randomized Participants
Timepoint [19] 0 0
24, 36, 48, 60, 72, and 84 months
Secondary outcome [20] 0 0
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led to Treatment Discontinuation at 24 Months of Follow-up
Timepoint [20] 0 0
Baseline to 30 days post last dose, up to 24 months
Secondary outcome [21] 0 0
Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) That Led toTreatment Discontinuation After 7 Year Follow-up
Timepoint [21] 0 0
Baseline to 30 days post last dose, up to 7 years (study closure July 2014)

Eligibility
Key inclusion criteria
For more information regarding BMS clinical trial participation, please visit
www.BMSStudyConnect.com.



- Subjects with Philadelphia chromosome positive (Ph+) (or BCR/ABL+) chronic phase
chronic myeloid leukemia whose disease has primary or acquired hematologic resistance
to imatinib mesylate or who are intolerant of imatinib mesylate.

- Men and women, 18 years 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.
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Women who are pregnant or breastfeeding

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

- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2014
Sample size
Target
Accrual to date
Final
724
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Local Institution - Camperdown
Recruitment hospital [2] 0 0
Local Institution - St Leonards
Recruitment hospital [3] 0 0
Local Institution - South Brisbane
Recruitment hospital [4] 0 0
Local Institution - Adelaide
Recruitment hospital [5] 0 0
Local Institution - East Melbourne
Recruitment hospital [6] 0 0
Local Institution - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
SA 5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3002 - East Melbourne
Recruitment postcode(s) [6] 0 0
WA 6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
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New York
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North Carolina
Country [19] 0 0
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Ohio
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Oregon
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Pennsylvania
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Tennessee
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Texas
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United States of America
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Washington
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Argentina
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Buenos Aires
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Argentina
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Capital Federal
Country [27] 0 0
Argentina
State/province [27] 0 0
Cordoba
Country [28] 0 0
Austria
State/province [28] 0 0
Wien
Country [29] 0 0
Belgium
State/province [29] 0 0
B-leuven
Country [30] 0 0
Belgium
State/province [30] 0 0
Brugge
Country [31] 0 0
Belgium
State/province [31] 0 0
Bruxelles
Country [32] 0 0
Belgium
State/province [32] 0 0
Charleroi
Country [33] 0 0
Belgium
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Edegem
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Belgium
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Yvoir
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Brazil
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Parana
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Brazil
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CEP - Campinas
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Brazil
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Rio de Janeiro
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Brazil
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San Paulo, Sp
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Brazil
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Sao Paulo
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Canada
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Alberta
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Ontario
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Quebec
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Czech Republic
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Brno
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Czech Republic
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Prague 2
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Denmark
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Aarhus C
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Denmark
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Herlev
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Denmark
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Odense C
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Finland
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Helsinki
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France
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Pierre Benite
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France
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Caen
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Creteil Cedex
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France
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Grenoble Cedex 09
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Lille Cedex
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France
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Marseille Cedex 9
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France
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Nantes
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France
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Paris Cedex 10
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France
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Poitiers Cedex
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France
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Strasbourg
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France
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Toulouse Cedex 9
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Germany
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Dresden
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Frankfurt/main
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Hamburg
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Leipzig
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Mainz
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Mannheim
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Bari
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Napoli
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Italy
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Roma
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Korea, Republic of
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Jeollanam-do
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Kyunggi-do
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Seoul
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Mexico
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Distrito Federal
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Netherlands
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Rotterdam
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Trondheim
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Lima
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Philippines
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Quezon City
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Gdansk
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Katowice
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Krakow
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Lodz
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Poland
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Lublin
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Poland
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Warsaw
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Russian Federation
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Moscow
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Russian Federation
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St.petersburg
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Singapore
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Singapore
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South Africa
State/province [93] 0 0
Free State
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South Africa
State/province [94] 0 0
Gauteng
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South Africa
State/province [95] 0 0
Western Cape
Country [96] 0 0
Spain
State/province [96] 0 0
Madrid
Country [97] 0 0
Spain
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Pamplona
Country [98] 0 0
Sweden
State/province [98] 0 0
Lund
Country [99] 0 0
Sweden
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Uppsala
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Switzerland
State/province [100] 0 0
Basel
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Taiwan
State/province [101] 0 0
Taipei
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Taiwan
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Taoyuan County
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Cambridgeshire
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United Kingdom
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Greater London
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United Kingdom
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Merseyside
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United Kingdom
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Tyne And Wear
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United Kingdom
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West Midlands
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United Kingdom
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Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Bristol-Myers Squibb
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase III study of BMS-354825 in subjects with chronic phase Philadelphia
chromosome or BCR-ABL positive chronic myelogenous leukemia, who are resistant or intolerant
to imatinib mesylate (Gleevec).
Trial website
https://clinicaltrials.gov/ct2/show/NCT00123474
Trial related presentations / publications
Porkka K, Khoury HJ, Paquette RL, Matloub Y, Sinha R, Cortes JE. Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion. Cancer. 2010 Jan 15;116(2):377-86. doi: 10.1002/cncr.24734.
Muller 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.
Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A, Khoroshko N, Paquette RL, Deininger M, Collins RH, Otero I, Hughes T, Bleickardt E, Strauss L, Francis S, Hochhaus A. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008 Jul 1;26(19):3204-12. doi: 10.1200/JCO.2007.14.9260. Epub 2008 Jun 9.
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries