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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/NCT00103844




Registration number
NCT00103844
Ethics application status
Date submitted
15/02/2005
Date registered
16/02/2005
Date last updated
10/08/2010

Titles & IDs
Public title
Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia
Scientific 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
Secondary ID [1] 0 0
CA180-017
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Myeloid Leukemia 0 0
Philadelphia-Positive Myeloid Leukemia 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
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

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

Experimental: 1 - Active Comparator

Experimental: 2 - Active Comparator


Treatment: Drugs: Dasatinib
Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks

Treatment: Drugs: Imatinib
Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Major Cytogenetic Response (MCyR) at Week 12
Timepoint [1] 0 0
Week 12
Secondary outcome [1] 0 0
MCyR at Any Time Prior to Crossover
Timepoint [1] 0 0
Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.
Secondary outcome [2] 0 0
Duration of MCyR at 12 Months and 18 Months
Timepoint [2] 0 0
12 months, 18 months
Secondary outcome [3] 0 0
Duration of MCyR at 24 Months
Timepoint [3] 0 0
24 Months
Secondary outcome [4] 0 0
Time to MCyR Prior to Crossover
Timepoint [4] 0 0
Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.
Secondary outcome [5] 0 0
Complete Hematologic Response (CHR) at Any Time Prior to Crossover
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Duration of Complete Hematologic Response (CHR)
Timepoint [6] 0 0
12 months, 24 months
Secondary outcome [7] 0 0
Time to CHR Prior to Crossover
Timepoint [7] 0 0
Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.
Secondary outcome [8] 0 0
Major Molecular Response (MMR)
Timepoint [8] 0 0
Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.
Secondary outcome [9] 0 0
CHR After Crossover
Timepoint [9] 0 0
Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.
Secondary outcome [10] 0 0
Cytogenetic Response After Crossover
Timepoint [10] 0 0
every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements
Secondary outcome [11] 0 0
Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover
Timepoint [11] 0 0
Continuously from baseline through 2 years
Secondary outcome [12] 0 0
Health-Related Quality of Life Prior to Crossover
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Timepoint [13] 0 0
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.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

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
Crossover
Other design features
Phase
Phase 2
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
1/02/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/03/2008
Sample size
Target
Accrual to date
Final
150
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,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 - Perth
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- St. Leonards
Recruitment postcode(s) [3] 0 0
- South Brisbane
Recruitment postcode(s) [4] 0 0
- Adelaide
Recruitment postcode(s) [5] 0 0
- Perth
Recruitment outside Australia
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United States of America
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Alabama
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California
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Greater London
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United Kingdom
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Tyne and Wear

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

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00103844
Trial related presentations / publications
Kantarjian H, Pasquini R, Levy 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.
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.
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00103844