Clinical trial NCT00103844: Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloid Leukemia
Philadelphia-Positive Myeloid Leukemia
Keywords: Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-02-16
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Major Cytogenetic Response (MCyR) at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: MCyR at Any Time Prior to Crossover
timeFrame: Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.
measure: Duration of MCyR at 12 Months and 18 Months
timeFrame: 12 months, 18 months
measure: Duration of MCyR at 24 Months
timeFrame: 24 Months
measure: Time to MCyR Prior to Crossover
timeFrame: Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.
measure: Complete Hematologic Response (CHR) at Any Time Prior to Crossover
timeFrame: 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.
measure: Duration of Complete Hematologic Response (CHR)
timeFrame: 12 months, 24 months
measure: Time to CHR Prior to Crossover
timeFrame: Baseline (within 4 weeks of Day 1), weekly until Week 12, then every 12 weeks until crossover or off-study; restricted to precrossover measurements.
measure: Major Molecular Response (MMR)
timeFrame: Pretreatment, then after every 4 weeks for 12 weeks, then after every 12 week period out to 2 years; restricted to precrossover measurements.
measure: CHR After Crossover
timeFrame: Weekly for 12 weeks, then after every 12 week period out to 2 years; restricted to postcrossover measurements.
measure: Cytogenetic Response After Crossover
timeFrame: every 12 week period out to 2 years and off-study timepoints; restricted to postcrossover measurements
measure: Adverse Events (AEs), Serious Adverse Events (SAEs), Deaths and Hematologic Toxicities Prior to Crossover
timeFrame: Continuously from baseline through 2 years
measure: Health-Related Quality of Life Prior to Crossover
timeFrame: 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.
measure: Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
timeFrame: 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.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution
state: Alabama
city: Anaheim
country: United States
facility: Local Institution
state: California
city: Bakersfield
country: United States
facility: Local Institution
state: California
city: Fullerton
country: United States
facility: Local Institution
state: California
city: Loma Linda
country: United States
facility: Local Institution
state: California
city: Los Angeles
country: United States
facility: Local Institution
state: California
city: Monterey Park
country: United States
facility: Local Institution
state: California
city: San Diego
country: United States
facility: Local Institution
state: California
city: Santa Barbara
country: United States
facility: Local Institution
state: California
city: Santa Maria
country: United States
facility: Local Institution
state: California
city: Stanford
country: United States
facility: Local Institution
state: California
city: Vallejo
country: United States
facility: Local Institution
state: California
city: Aurora
country: United States
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state: Colorado
city: Hartford
country: United States
facility: Local Institution
state: Connecticut
city: Washington
country: United States
facility: Local Institution
state: District of Columbia
city: Jacksonville
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state: Florida
city: Tampa
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state: Florida
city: Athens
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state: Georgia
city: Atlanta
country: United States
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state: Georgia
city: Lawrenceville
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state: Georgia
city: Tucker
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state: Georgia
city: Chicago
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state: Illinois
city: Peoria
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state: Illinois
city: Indianapolis
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state: Indiana
city: Kansas City
country: United States
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state: Kansas
city: Lexington
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state: Kentucky
city: Boston
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state: Massachusetts
city: Minneapolis
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state: Minnesota
city: Rochester
country: United States
facility: Local Institution
state: Minnesota
city: Columbia
country: United States
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state: Missouri
city: Kansas City
country: United States
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state: Missouri
city: St. Louis
country: United States
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state: Missouri
city: Omaha
country: United States
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state: Nebraska
city: Hackensack
country: United States
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state: New Jersey
city: Morristown
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state: New Jersey
city: New Brunswick
country: United States
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state: New Jersey
city: Cary
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state: North Carolina
city: Chapel Hill
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state: North Carolina
city: Oklahoma City
country: United States
facility: Local Institution
state: Oklahoma
city: Tulsa
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state: Oklahoma
city: Portland
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state: Oregon
city: Pittsburgh
country: United States
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state: Pennsylvania
city: Greenville
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state: South Carolina
city: Nashville
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city: Dallas
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state: Texas
city: Fort Worth
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city: Houston
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city: San Antonio
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city: Tyler
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state: Texas
city: Norfolk
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state: Virginia
city: Seattle
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state: Washington
city: Spokane
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state: Washington
city: Vancouver
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state: Washington
city: Buenos Aires
country: Argentina
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city: Cordoba
country: Argentina
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city: Camperdown
country: Australia
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state: New South Wales
city: St. Leonards
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
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state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Wein
country: Austria
facility: Local Institution
city: B-Leuven
country: Belgium
facility: Local Institution
city: Brugge
country: Belgium
facility: Local Institution
city: Bruxelles
country: Belgium
facility: Local Institution
city: Charleroi
country: Belgium
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city: Edegem
country: Belgium
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city: Yvoir
country: Belgium
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city: Curitiba
country: Brazil
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state: Parana
city: Rio De Janeiro
country: Brazil
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city: Sao Paulo
country: Brazil
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city: Edmonton
country: Canada
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state: Alberta
city: Vancouver
country: Canada
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state: British Columbia
city: Toronto
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state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Beijing
country: China
facility: Local Institution
city: Shanghai
country: China
facility: Local Institution
city: Aarhus
country: Denmark
facility: Local Institution
city: Tallin
country: Estonia
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Lille
country: France
facility: Local Institution
city: Lyon Cedex 03
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Poitiers
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Groenkloof
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Mainz
country: Germany
facility: Local Institution
city: Mannheim
country: Germany
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
city: Ramat-Gan
country: Israel
facility: Local Institution
city: Bari
country: Italy
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Milano
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Orbassano
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Kyunggi-Do
country: Korea, Republic of
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Warsaw
country: Poland
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St. Petersburg
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: Free State
city: Parktown
country: South Africa
facility: Local Institution
state: Gauteng
city: Soweto
country: South Africa
facility: Local Institution
state: Gauteng
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Gothenburg
country: Sweden
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Stockholm
country: Sweden
facility: Local Institution
city: Umea
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Basel
country: Switzerland
facility: Local Institution
city: Bellinzona
country: Switzerland
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taoyuan
country: Taiwan
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Glasglow
country: United Kingdom
facility: Local Institution
state: Central
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Newcastle
country: United Kingdom
facility: Local Institution
state: Tyne and Wear
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.