Dasatinib (BMS-354835) Versus Imatinib Mesylate in Subjects With Chronic Myeloid Leukemia

NCT00103844 | Completed Phase 2 Results

• 1 other identifier: CA180-017
• Study Type: interventional
• Target: 150
• Locations: 30 countries
• Sites: 129

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.

Conditions

Chronic Myeloid Leukemia; Philadelphia-Positive Myeloid Leukemia

Keywords

Chronic Phase Philadelphia chromosome Positive (Ph+) chronic myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Major Cytogenetic Response (MCyR) at Week 12

  Cytogenetic response was based on the prevalence of Philadelphia chromosome positive (Ph+) metaphases among cells in metaphase on a bone marrow sample (aspirate/biopsy). MCyR was defined as Complete CyR (CCyR; 0% Ph+ cells in metaphase in bone marrow) or Partial CyR (PCyR; \>0% to 35% Ph+ cells in metaphase in bone marrow).

  Week 12

Secondary Outcomes (13)

• MCyR at Any Time Prior to Crossover

  Baseline (within 4 weeks of Day 1), every 12 weeks until crossover or off-study timepoints. Restricted to precrossover measurements.

• Duration of MCyR at 12 Months and 18 Months

  12 months, 18 months

• Duration of MCyR at 24 Months

  24 Months

• Time to MCyR Prior to Crossover

  Baseline (within 4 weeks of Day 1), every 12 weeks, at crossover or off-study timepoints; restricted to precrossover measurements.

• Complete Hematologic Response (CHR) at Any Time Prior to Crossover

  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.

Study Arms (2)

1

EXPERIMENTAL

Active Comparator

Drug: Dasatinib

2

EXPERIMENTAL

Active Comparator

Drug: Imatinib

Interventions

Dasatinib DRUG

Tablets, oral, 20 mg and 50mg, twice daily, up to 96 weeks

Also known as: Sprycel, BMS-354825

1

Imatinib DRUG

Tablets, Oral, 400mg and 100mg, twice daily, up to 96 weeks

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (131)

Local Institution

Birmingham, Alabama, United States

Location

Local Institution

Anaheim, California, United States

Location

Local Institution

Bakersfield, California, United States

Location

Local Institution

Fullerton, California, United States

Location

Local Institution

Loma Linda, California, United States

Location

Local Institution

Los Angeles, California, United States

Location

Local Institution

Monterey Park, California, United States

Location

Local Institution

San Diego, California, United States

Location

Local Institution

Santa Barbara, California, United States

Location

Local Institution

Santa Maria, California, United States

Location

Local Institution

Stanford, California, United States

Location

Local Institution

Vallejo, California, United States

Location

Local Institution

Aurora, Colorado, United States

Location

Local Institution

Hartford, Connecticut, United States

Location

Local Institution

Washington D.C., District of Columbia, United States

Location

Local Institution

Jacksonville, Florida, United States

Location

Local Institution

Tampa, Florida, United States

Location

Local Institution

Athens, Georgia, United States

Location

Local Institution

Atlanta, Georgia, United States

Location

Local Institution

Lawrenceville, Georgia, United States

Location

Local Institution

Tucker, Georgia, United States

Location

Local Institution

Chicago, Illinois, United States

Location

Local Institution

Peoria, Illinois, United States

Location

Local Institution

Indianapolis, Indiana, United States

Location

Local Institution

Kansas City, Kansas, United States

Location

Local Institution

Lexington, Kentucky, United States

Location

Local Institution

Boston, Massachusetts, United States

Location

Local Institution

Minneapolis, Minnesota, United States

Location

Local Institution

Rochester, Minnesota, United States

Location

Local Institution

Columbia, Missouri, United States

Location

Local Institution

Kansas City, Missouri, United States

Location

Local Institution

St Louis, Missouri, United States

Location

Local Institution

Omaha, Nebraska, United States

Location

Local Institution

Hackensack, New Jersey, United States

Location

Local Institution

Morristown, New Jersey, United States

Location

Local Institution

New Brunswick, New Jersey, United States

Location

Local Institution

Cary, North Carolina, United States

Location

Local Institution

Chapel Hill, North Carolina, United States

Location

Local Institution

Oklahoma City, Oklahoma, United States

Location

Local Institution

Tulsa, Oklahoma, United States

Location

Local Institution

Portland, Oregon, United States

Location

Local Institution

Pittsburgh, Pennsylvania, United States

Location

Local Institution

Greenville, South Carolina, United States

Location

Local Institution

Nashville, Tennessee, United States

Location

Local Institution

Dallas, Texas, United States

Location

Local Institution

Fort Worth, Texas, United States

Location

Local Institution

Houston, Texas, United States

Location

Local Institution

San Antonio, Texas, United States

Location

Local Institution

Tyler, Texas, United States

Location

Local Institution

Norfolk, Virginia, United States

Location

Local Institution

Seattle, Washington, United States

Location

Local Institution

Spokane, Washington, United States

Location

Local Institution

Vancouver, Washington, United States

Location

Local Institution

Buenos Aires, Buenos Aires, Argentina

Location

Local Institution

Córdoba, Córdoba Province, Argentina

Location

Local Institution

Camperdown, New South Wales, Australia

Location

Local Institution

St Leonards, New South Wales, Australia

Location

Local Institution

South Brisbane, Queensland, Australia

Location

Local Institution

Adelaide, South Australia, Australia

Location

Local Institution

Perth, Western Australia, Australia

Location

Local Institution

Wein, Austria

Location

Local Institution

B-Leuven, Belgium

Location

Local Institution

Bruges, Belgium

Location

Local Institution

Brussels, Belgium

Location

Local Institution

Charleroi, Belgium

Location

Local Institution

Edegem, Belgium

Location

Local Institution

Yvoir, Belgium

Location

Local Institution

Curitiba, Paraná, Brazil

Location

Local Institution

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Local Institution

São Paulo, São Paulo, Brazil

Location

Local Institution

Edmonton, Alberta, Canada

Location

Local Institution

Vancouver, British Columbia, Canada

Location

Local Institution

Toronto, Ontario, Canada

Location

Local Institution

Montreal, Quebec, Canada

Location

Local Institution

Beijing, China

Location

Local Institution

Shanghai, China

Location

Local Institution

Aarhus, Denmark

Location

Local Institution

Tallinn, Estonia

Location

Local Institution

Helsinki, Finland

Location

Local Institution

Lille, France

Location

Local Institution

Lyon, France

Location

Local Institution

Nantes, France

Location

Local Institution

Paris, France

Location

Local Institution

Pessac, France

Location

Local Institution

Poitiers, France

Location

Local Institution

Strasbourg, France

Location

Local Institution

Dresden, Germany

Location

Local Institution

Groenkloof, Germany

Location

Local Institution

Hamburg, Germany

Location

Local Institution

Leipzig, Germany

Location

Local Institution

Mainz, Germany

Location

Local Institution

Mannheim, Germany

Location

Local Institution

Budapest, Hungary

Location

Local Institution

Dublin, Ireland

Location

Local Institution

Ramat Gan, Israel

Location

Local Institution

Bari, Italy

Location

Local Institution

Bologna, Italy

Location

Local Institution

Milan, Italy

Location

Local Institution

Napoli, Italy

Location

Local Institution

Orbassano, Italy

Location

Local Institution

Roma, Italy

Location

Local Institution

Trondheim, Norway

Location

Local Institution

Lima, Lima Province, Peru

Location

Local Institution

Quezon City, Philippines

Location

Local Institution

Katowice, Poland

Location

Local Institution

Krakow, Poland

Location

Local Institution

Lublin, Poland

Location

Local Institution

Warsaw, Poland

Location

Local Institution

San Juan, Puerto Rico

Location

Local Institution

Moscow, Russia

Location

Local Institution

Saint Petersburg, Russia

Location

Local Institution

Singapore, Singapore

Location

Local Institution

Bloemfontein, Free State, South Africa

Location

Local Institution

Parktown, Gauteng, South Africa

Location

Local Institution

Soweto, Gauteng, South Africa

Location

Local Institution

Kyunggi-Do, South Korea

Location

Local Institution

Barcelona, Spain

Location

Local Institution

Madrid, Spain

Location

Local Institution

Gothenburg, Sweden

Location

Local Institution

Lund, Sweden

Location

Local Institution

Stockholm, Sweden

Location

Local Institution

Umeå, Sweden

Location

Local Institution

Uppsala, Sweden

Location

Local Institution

Basel, Switzerland

Location

Local Institution

Bellinzona, Switzerland

Location

Local Institution

Taipei, Taiwan

Location

Local Institution

Taoyuan District, Taiwan

Location

Local Institution

Bangkok, Thailand

Location

Local Institution

Glasglow, Central, United Kingdom

Location

Local Institution

London, Greater London, United Kingdom

Location

Local Institution

Newcastle, Tyne and Wear, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 19536906 BACKGROUND

• 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.

  PMID: 19779040 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Dasatinib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 15, 2005
• First Posted: February 16, 2005
• Study Start: February 1, 2005
• Primary Completion: August 1, 2006
• Study Completion: March 1, 2008
• Last Updated: August 10, 2010
• Results First Posted: January 7, 2010

Record last verified: 2010-06

Locations

CN (2); CA (4); ES (2); IL (1); ZA (3); RU (2); SG (1); FR (7); PE (1); BE (6); PR (1); CH (2); AU (5); DE (6); US (53); PH (1); GB (3); TH (1); SE (5); KR (1); NO (1); PL (4); FI (1); BR (3); IE (1); IT (6); DK (1); TW (2); HU (1); AR (2)