Advanced Chronic Myelogenous Leukemia (CML) - Follow On: Study of BMS-354825 in Subjects With CML
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)
1 other identifier
interventional
638
31 countries
114
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2005
Longer than P75 for phase_3
114 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
June 1, 2005
CompletedFirst Submitted
Initial submission to the registry
July 21, 2005
CompletedFirst Posted
Study publicly available on registry
July 25, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2006
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2013
CompletedResults Posted
Study results publicly available
October 22, 2014
CompletedNovember 3, 2014
October 1, 2014
1.4 years
July 21, 2005
October 16, 2014
October 30, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percent of Participants With Major Hematologic Response (MaHR) With 6 Months of Follow-up From Date of Last Enrollment - Randomized Population
MaHR defined by either complete hematologic response (CHR) or no evidence of leukemia (NEL). CHR defined as: white blood cells (WBC) ≤ upper limit of normal (ULN); absolute neutrophil count (ANC) ≥ 1,000/mm\^3; platelets ≥ 100,000/mm\^3; no blasts or promyelocytes in peripheral blood (PB); bone marrow (BM) blasts ≤ 5%; \<5% myelocytes plus metamyelocytes in PB; basophils in PB \< 20%; no extra-medullar involvement (including no hepatomegaly or splenomegaly). NEL defined by same criteria as CHR except that platelets and ANC had to satisfy at least one of the following (note that both lower limits had to be satisfied): platelets ≥ 20,000/mm\^3 and \< 100,000/mm\^3; ANC \> 500/mm\^3 and \<1,000/mm\^3. After Year 2, Amendment 3 allowed participants to switch from the BID to the QD dosing schedule. Percentage: number of participants with MaHR/number of randomized participants.
Randomization up to 6 months
Secondary Outcomes (17)
Percent of Participants With Major Hematological Response (MaHR) With 2 Years of Follow-up From Date of Last Enrollment - Randomized Population
Randomization up to 2 years
Percent of Participants With Major Hematologic Response (MaHR) by Disease Group - Randomized Population
Randomization up to 2 years
Median Time to Major Hematologic Response (MaHR) - Randomized Population
Day 1 up to 6 months (time of primary endpoint), 2 years
Median Duration of a Major Hematologic Response (MaHR) in Those Participants Who Achieved a MaHR During the Study
Day 1 up to 5 years
Percent of Participants With Overall Hematologic Response - Randomized Population
Randomization up to 6 Months, 2 Years
- +12 more secondary outcomes
Study Arms (2)
dasatinib Twice a Day (BID)
EXPERIMENTAL70 mg dasatinib twice a day (BID)
dasatinib Once a Day (QD)
EXPERIMENTAL140 mg dasatinib once a day (QD)
Interventions
Tablets, Oral, 70 mg BID, indefinitely, survival study
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (119)
University Of Alabama At Birmingham
Birmingham, Alabama, 35294, United States
Loma Linda University Cancer Center
Loma Linda, California, 92354, United States
Ucla Dept. Of Medicine
Los Angeles, California, 90095, United States
Washington Cancer Institute At Washington Hospital Center
Washington D.C., District of Columbia, 20010, United States
University Of Miami
Miami, Florida, 33136, United States
Emory University School Of Medicine
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
The University Of Chicago
Chicago, Illinois, 60637-1463, United States
Indiana University Cancer Center
Indianapolis, Indiana, 46202, United States
University Of Kentucky
Lexington, Kentucky, 40536-0098, United States
University Of Maryland
Baltimore, Maryland, 21201-1595, United States
Dana Faber Cancer Institute
Boston, Massachusetts, 02115, United States
Karmanos Cancer Center
Detroit, Michigan, 48201, United States
Washington University School Of Medicine
St Louis, Missouri, 63110-1093, United States
Nebraska Methodist Hospital
Omaha, Nebraska, 68114, United States
Devetten, Marcel
Omaha, Nebraska, 68198-7680, United States
The Cancer Center At Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
The Cancer Institute Of New Jersey
New Brunswick, New Jersey, 08903, United States
New York Presbyterian Hospital
New York, New York, 10021, United States
The University Of North Carolina At Chapel Hill
Chapel Hill, North Carolina, 27599-7305, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Oregon Health & Sci Univ
Portland, Oregon, 97239, United States
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, 15224, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
The University Of Texas Md Anderson Cancer Center
Houston, Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Local Institution
Capital Federal, Buenos Aires, 1280, Argentina
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St Leonards, New South Wales, 2065, Australia
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South Brisbane, Queensland, 4101, Australia
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Adelaide, South Australia, SA 5000, Australia
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Parkville, Victoria, 3050, Australia
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Perth, Western Australia, WA 6000, Australia
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Vienna, 1090, Austria
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B-leuven, 3000, Belgium
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Bruges, 8000, Belgium
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Brussels, 1000, Belgium
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Charleroi, 6000, Belgium
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Yvoir, 5530, Belgium
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Curitiba, Paraná, 80060-900, Brazil
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Campinas, São Paulo, 13083-970, Brazil
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Morumbi, São Paulo, 05652-000, Brazil
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São Paulo, São Paulo, 05403-000, Brazil
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Rio de Janeiro, 20230-130, Brazil
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Edmonton, Alberta, T6G 1Z2, Canada
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Vancouver, British Columbia, V5Z 1M9, Canada
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Montreal, Quebec, H3A 1A1, Canada
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Brno, 62500, Czechia
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Prague, 128 20, Czechia
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Aarhus C, Denmark, 8000, Denmark
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Herlev, 2730, Denmark
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Odense C, 5000, Denmark
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Helsinki, 00029, Finland
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Caen, 14033, France
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Créteil, 94010, France
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Grenoble, 38043, France
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Lille, 59037, France
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Lyon, 69437, France
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Marseille, 13273, France
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Nantes, 44000, France
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Paris, 75475, France
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Pessac, 33604, France
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Poitiers, 86021, France
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Strasbourg, 67091, France
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Dresden, 01307, Germany
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Frankfurt, 60596, Germany
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Hamburg, 20246, Germany
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Leipzig, 04103, Germany
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Mainz, 55131, Germany
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Mannheim, 68167, Germany
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Athens, 11523, Greece
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Budapest, 1135, Hungary
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Dublin, Ireland
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Ramat Gan, 52621, Israel
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Bari, 70124, Italy
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Bologna, 40138, Italy
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Monza, 20052, Italy
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Napoli, 80131, Italy
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Orbassano (to), 10043, Italy
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Roma, 00144, Italy
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Rotterdam, 3075 EA, Netherlands
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Trondheim, 7006, Norway
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Lima, Lima Province, 34, Peru
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Jesus Maria, Lima region, 11, Peru
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Quezon City, 1102, Philippines
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Gdansk, 80211, Poland
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Katowice, 40032, Poland
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Krakow, 31501, Poland
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Lodz, 93510, Poland
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Lublin, 20950, Poland
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Warsaw, 02097, Poland
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Moscow, 125167, Russia
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Saint Petersburg, 197022, Russia
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Singapore, 169608, Singapore
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Bloemfontein, Free State, 9301, South Africa
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Groenkloof, Gauteng, 0181, South Africa
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Parktown, Gauteng, 2193, South Africa
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Observatory, Western Cape, 7925, South Africa
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Jeollanam-do, South Korea
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Seoul, 110-744, South Korea
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Seoul, 137-040, South Korea
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Seoul, 138-736, South Korea
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Barcelona, 08036, Spain
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Madrid, 28006, Spain
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Madrid, 28034, Spain
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Valencia, 46009, Spain
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Lund, 22185, Sweden
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Stockholm, 17176, Sweden
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Umeå, 90185, Sweden
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Uppsala, 75185, Sweden
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Basel, 4031, Switzerland
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Taipei, 100, Taiwan
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Taipei, Taiwan
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Taoyuan District, 333, Taiwan
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Bangkok, 10400, Thailand
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London, Greater London, W12 ONN, United Kingdom
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Glasgow, Scotland, G12 OXB, United Kingdom
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Newcastle, Tyne and Wear, NE2 4HH, United Kingdom
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Edinburgh, EH8 9RS, United Kingdom
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Liverpool, L7 8XP, United Kingdom
Related Publications (3)
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.
PMID: 16960978RESULTLilly 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.
PMID: 20131302DERIVEDKantarjian 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.
PMID: 19369231DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Amendment 3 (7 March 2007) allowed participants to switch from BID to QD dosing. Therefore, results for BID summarized by treatment group after Year 2 may not be a complete reflection of the BID experience and should be interpreted with this in mind.
Results Point of Contact
- Title
- : Bristol-Myers Squibb Study Director
- Organization
- Bristol-Myers Squibb
Study Officials
- STUDY DIRECTOR
Bristol-Myers Squibb
Bristol-Myers Squibb
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2005
First Posted
July 25, 2005
Study Start
June 1, 2005
Primary Completion
November 1, 2006
Study Completion
June 1, 2013
Last Updated
November 3, 2014
Results First Posted
October 22, 2014
Record last verified: 2014-10