Clinical trial NCT00123487: Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML
Official title: A Randomized Two-Arm, Multicenter, Open-Label Phase III Study of BMS-354825 Administered Orally at a Dose of 70 mg Twice Daily or 140 mg Once Daily in Subjects With Chronic Myeloid Leukemia in Accelerated Phase or in Myeloid or Lymphoid Blast Phase or With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Who Are Resistant or Intolerant to Imatinib Mesylate (Gleevec)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myeloid Leukemia, Chronic, Accelerated Phase
Leukemia, Lymphoblastic, Acute, Philadelphia-Positive
Keywords: Accelerated Phase Chronic Myeloid Leukemia
Lymphoid Blast Phase Chronic Myeloid Leukemia
Myeloid Blast Phase Chronic Myeloid Leukemia
Philadelphia Positive Acute Lymphoblastic Leukemia
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2005-07-25
Enrollment: 638
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III study of BMS-354825 in subjects with chronic myelogenous leukemia in accelerated phase, or in myeloid or lymphoid blast phase or with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia who are resistant or intolerant to imatinib mesylate (Gleevec).


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

Inclusion Criteria:

* Patients with Philadelphia-Positive (Ph+) (or BCR/ABL+) accelerated phase chronic myeloid leukemia, Ph+ (or BCR/ABL+) blast phase chronic myeloid leukemia, or Ph+ (or BCR/ABL+) acute lymphoblastic leukemia whose disease has primary or acquired hematologic resistance to imatinib mesylate or who are intolerant of imatinib mesylate
* Men and women, 18 years of age 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
* Eastern Cooperative Oncology Group (ECOG) performance status score 0 - 2

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* 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
* Prior therapy with BMS-35425
* 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

Primary outcomes:
measure: Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population
timeFrame: Randomization up to 6 months
Secondary outcomes:
measure: Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population
timeFrame: Randomization up to 2 years
measure: Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population
timeFrame: Randomization up to 2 years
measure: Median Time to Major Hematologic Response (MaHR) - Randomized Population
timeFrame: Day 1 up to 6 months (time of primary endpoint), 2 years
measure: Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study
timeFrame: Day 1 up to 5 years
measure: Percent of Participants With Overall Hematologic Response - Randomized Population
timeFrame: Randomization up to 6 Months, 2 Years
measure: Number of Participants With Best Confirmed Hematologic Response, Major Hematologic Response (MaHR) and Overall Hematologic Response - Randomized Population
timeFrame: Randomization up to 6 months, 2 years
measure: Percent of Participants With Major Cytogenetic Response (MCyR) - Randomized Population
timeFrame: Randomization up to 6 Months, 2 Years
measure: Number of Participants With Best Cytogenic Response (CyR) - Randomized Population
timeFrame: Randomization up to 6 Months, 2 Years
measure: Median Progression Free Survival (PFS) - Randomized Population
timeFrame: Randomization up to 5 Years
measure: Median Overall Survival (OS) - Randomized Population
timeFrame: Randomization up to 5 Years
measure: Progression Free Survival (PFS) and Overall Survival (OS) at 24, 36, 48, and 60 Months - Randomized Population
timeFrame: 24 months, 36 months, 48 months, 60 months
measure: Number of Participants With Death, Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation and Drug-related Fluid Retention AEs, up to Year 7 in Treated Participants
timeFrame: Day 1 to Year 7
measure: Number of Participants With Normal Baseline Versus Worst Grade 3/4 Hematology Laboratory Abnormalities up to Year 2 in Treated Participants
timeFrame: Baseline to Year 2
measure: Number of Participants With Grade 4 Myelosuppression Determined From Hematology Evaluations
timeFrame: Day 1 up to Year 7
measure: Number of Participants With Normal Baseline Versus Worst Grade 3/4 Biochemistry Laboratory Abnormalities up to Year 2 in Treated Participants
timeFrame: Baseline to Year 2
measure: Number of Participants With Changes From Baseline in QT Interval Corrected With Fridericia Formula (QTcF) up to Year 2 in Treated Participants
timeFrame: Baseline to Year 2
measure: Number of Participants With Maximal QTcF Intervals up to Year 2 in Treated Participants
timeFrame: Baseline up to Year 2
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Of Alabama At Birmingham
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Center
state: California
city: Los Angeles
country: United States
facility: Ucla Dept. Of Medicine
state: California
city: Washington
country: United States
facility: Washington Cancer Institute At Washington Hospital Center
state: District of Columbia
city: Miami
country: United States
facility: University Of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University School Of Medicine
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: The University Of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Lexington
country: United States
facility: University Of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: University Of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Omaha
country: United States
facility: Devetten, Marcel
state: Nebraska
city: Hackensack
country: United States
facility: The Cancer Center At Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: The Cancer Institute Of New Jersey
state: New Jersey
city: New York
country: United States
facility: New York Presbyterian Hospital
state: New York
city: Chapel Hill
country: United States
facility: The University Of North Carolina At Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Sci Univ
state: Oregon
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: St Leonards
country: Australia
facility: Local Institution
state: New South Wales
city: South Brisbane
country: Australia
facility: Local Institution
state: Queensland
city: Adelaide
country: Australia
facility: Local Institution
state: South Australia
city: Parkville
country: Australia
facility: Local Institution
state: Victoria
city: Perth
country: Australia
facility: Local Institution
state: Western Australia
city: Wien
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
facility: Local Institution
city: Yvoir
country: Belgium
facility: Local Institution
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Morumbi
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Brno
country: Czech Republic
facility: Local Institution
city: Prague 2
country: Czech Republic
facility: Local Institution
city: Aarhus C
country: Denmark
facility: Local Institution
city: Herlev
country: Denmark
facility: Local Institution
city: Odense C
country: Denmark
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Caen Cedex
country: France
facility: Local Institution
city: Creteil Cedex
country: France
facility: Local Institution
city: Grenoble Cedex 9
country: France
facility: Local Institution
city: Lille Cedex
country: France
facility: Local Institution
city: Lyon Cedex
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Nantes
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: Poitiers Cedex
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Dresden
country: Germany
facility: Local Institution
city: Frankfurt
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: Athens
country: Greece
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: Monza
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Orbassano (to)
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Jeollanam-do
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Rotterdam
country: Netherlands
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Jesus Maria
country: Peru
facility: Local Institution
state: Lima
city: Lima
country: Peru
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Gdansk
country: Poland
facility: Local Institution
city: Katowice
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Lublin
country: Poland
facility: Local Institution
city: Warsaw
country: Poland
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: Groenkloof
country: South Africa
facility: Local Institution
state: Gauteng
city: Parktown
country: South Africa
facility: Local Institution
state: Gauteng
city: Observatory
country: South Africa
facility: Local Institution
state: Western Cape
city: Barcelona
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Valencia
country: Spain
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: Taipei
country: Taiwan
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: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Scotland
city: Newcastle
country: United Kingdom
facility: Local Institution
state: Tyne And Wear
city: Edinburgh
country: United Kingdom
facility: Local Institution
city: Liverpool
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Chu SC, Tang JL, Li CC. Dasatinib in chronic myelogenous leukemia. N Engl J Med. 2006 Sep 7;355(10):1062-3; author reply 1063-4. No abstract available.
citation: Lilly MB, Ottmann OG, Shah NP, Larson RA, Reiffers JJ, Ehninger G, Muller MC, Charbonnier A, Bullorsky E, Dombret H, Brigid Bradley-Garelik M, Zhu C, Martinelli G. Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study. Am J Hematol. 2010 Mar;85(3):164-70. doi: 10.1002/ajh.21615.
citation: Kantarjian H, Cortes J, Kim DW, Dorlhiac-Llacer P, Pasquini R, DiPersio J, Muller MC, Radich JP, Khoury HJ, Khoroshko N, Bradley-Garelik MB, Zhu C, Tallman MS. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009 Jun 18;113(25):6322-9. doi: 10.1182/blood-2008-11-186817. Epub 2009 Apr 15.