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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00101660




Registration number
NCT00101660
Ethics application status
Date submitted
12/01/2005
Date registered
13/01/2005
Date last updated
2/03/2012

Titles & IDs
Public title
Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib
Scientific title
A Phase II Study to Determine the Activity of BMS-354825 in Subjects With Chronic Phase Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Have Disease That is Resistant to High Dose Imatinib Mesylate (Gleevec) or Who Are Intolerant of Imatinib
Secondary ID [1] 0 0
CA180-013
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

Experimental: Dasatinib, 70 mg twice daily (BID) - Dasatanib, 70 mg twice daily (BID), with dose escalation to 90 mg BID was allowed for participants who showed evidence of progression or lack of response. Up to 2 dose reductions were allowed for intolerance.


Treatment: Drugs: Dasatinib
Tablets; oral; 70 mg BID, depending on response
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Number of Imatinib-intolerant Participants With MCyR
Timepoint [1] 0 0
Baseline to 2 years
Secondary outcome [2] 0 0
Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months
Timepoint [2] 0 0
12 and 24 Months
Secondary outcome [3] 0 0
Median Time From First Dosing Date to Date of MCyR
Timepoint [3] 0 0
Baseline (within 4 weeks of Day 1) and every 12 weeks
Secondary outcome [4] 0 0
Number of Participants With Complete Hematologic Response (CHR)
Timepoint [4] 0 0
Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Secondary outcome [5] 0 0
Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months
Timepoint [5] 0 0
12 and 24 months
Secondary outcome [6] 0 0
Median Time From First Dosing Until CHR
Timepoint [6] 0 0
Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Secondary outcome [7] 0 0
Number of Participants With Major Molecular Response (MMR)
Timepoint [7] 0 0
Baseline to 2 years
Secondary outcome [8] 0 0
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Timepoint [8] 0 0
Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.
Secondary outcome [9] 0 0
Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE
Timepoint [9] 0 0
Continuously, from baseline through 2 years
Secondary outcome [10] 0 0
Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE
Timepoint [10] 0 0
Continuously, from baseline through 2 years
Secondary outcome [11] 0 0
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Timepoint [11] 0 0
Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.

Eligibility
Key inclusion criteria
* Age of 18 years and older.
* Chronic myeloid leukemia (CML)
* Previous treatment with imatinib at a dose of >600 mg/day AND the development of progressive disease while receiving imatinib at that dose, OR
* CML with resistance to imatinib at a dose less than or equal to 600 mg/day with genetic mutation in the BCR-ABL gene that is associated with a high level of resistance to imatinib, OR
* Intolerance to imatinib at any dose
* Adequate organ function
* Women who are able to bear children must have a negative serum or urine pregnancy test. Adequate methods of contraception must be used throughout the study to avoid pregnancy for the entire interval of at least 1 month before and 3 months after completion of the study medication.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Woman who are pregnant or breastfeeding
* Men whose sexual partners are women who are of childbearing potential, and who are unwilling or unable to use an acceptable method to avoid pregnancy of his partner for the entire study period as outlined above
* Previous diagnosis of accelerated phase or blast crisis CML.
* Participants who are eligible and willing to undergo transplantation during the screening period
* Uncontrolled or significant cardiovascular disease
* Use of imatinib within 7 days.
* Use of interferon or cytarabine within 14 days
* Use of a targeted small-molecule anticancer agent within 14 days
* Use of certain medication that carry a known side effect risk of Torsade de Pointes - Certain medications that irreversibly inhibit platelet function or anticoagulants
* Prior therapy with dasatinib.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Single group
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
1/04/2008
Sample size
Target
Accrual to date
Final
387
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Local Institution - St. Leonards
Recruitment hospital [2] 0 0
Local Institution - South Brisbane
Recruitment hospital [3] 0 0
Local Institution - Adelaide
Recruitment hospital [4] 0 0
Local Institution - East Mebourne
Recruitment hospital [5] 0 0
Local Institution - Parkville
Recruitment postcode(s) [1] 0 0
- St. Leonards
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Adelaide
Recruitment postcode(s) [4] 0 0
- East Mebourne
Recruitment postcode(s) [5] 0 0
- Parkville
Recruitment outside Australia
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United States of America
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California
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Connecticut
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District of Columbia
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Wein
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Belgium
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Edegem
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Israel
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Bari
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Bologna
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Italy
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Roma
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Korea, Republic of
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Kyunggi-Do
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Netherlands
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Nijmegen
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Rotterdam
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Trondheim
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Lima
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Singapore
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Umea
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Uppsala
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Switzerland
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Basel
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United Kingdom
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Central
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United Kingdom
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Greater London

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

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is assess the effects of the investigational drug dasatinib on participants who are in chronic phase Philadelphia chromosome chronic myeloid leukemia and who are either resistant to or intolerant of imatinib. Other purposes of the study are to identify any side effects the drug may produce and to study the level of dasatanib in the blood and assess the efficacy of dasatanib in the treatment of leukemia.
Trial website
https://clinicaltrials.gov/study/NCT00101660
Trial related presentations / publications
Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, Facon T, Goldberg SL, Cervantes F, Niederwieser D, Silver RT, Stone RM, Hughes TP, Muller MC, Ezzeddine R, Countouriotis AM, Shah NP. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007 Mar 15;109(6):2303-9. doi: 10.1182/blood-2006-09-047266. Epub 2006 Nov 30. Erratum In: Blood. 2007 Sep 1;110(5):1438.
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/study/NCT00101660