Study of BMS-354825 (Dasatinib) in Patients With Chronic Myeloid Leukemia Who Are Either Resistant or Intolerant to Imatinib

NCT00101660 | Completed Phase 2 Results

• 1 other identifier: CA180-013
• Study Type: interventional
• Target: 387
• Locations: 21 countries
• Sites: 80

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.

Conditions

Chronic Myeloid Leukemia; Philadelphia-Positive Myeloid Leukemia

Keywords

Chronic phase Philadelphia chromosome chronic myeloid leukemia (Ph+CML)

Outcome Measures

Primary Outcomes (1)

• Number of Imatinib-resistant Participants With Major Cytogenetic Response (MCyR)

  Cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of Complete Cytogenetic Response (CCyR)-0% Ph+ metaphases plus Partial Cytogenetic Response (PCyR)-1% to 35% Ph+ metaphases.

  2 years

Secondary Outcomes (11)

• Number of Imatinib-intolerant Participants With MCyR

  Baseline to 2 years

• Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months

  12 and 24 Months

• Median Time From First Dosing Date to Date of MCyR

  Baseline (within 4 weeks of Day 1) and every 12 weeks

• Number of Participants With Complete Hematologic Response (CHR)

  Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study

• Percentage of Participants Who Acheived CHR and Did Not Progress at 12 Months and 24 Months

  12 and 24 months

Study Arms (1)

Dasatinib, 70 mg twice daily (BID)

EXPERIMENTAL

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.

Drug: Dasatinib

Interventions

Dasatinib DRUG

Tablets; oral; 70 mg BID, depending on response

Dasatinib, 70 mg twice daily (BID)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (85)

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Anaheim, California, United States

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Loma Linda, California, United States

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Los Angeles, California, United States

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Stanford, California, United States

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Vallejo, California, United States

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Hartford, Connecticut, United States

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

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Jacksonville, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Kansas City, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Hackensack, New Jersey, United States

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New Brunswick, New Jersey, United States

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New York, New York, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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San Antonio, Texas, United States

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Tyler, Texas, United States

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Spokane, Washington, United States

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St Leonards, New South Wales, Australia

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South Brisbane, Queensland, Australia

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Adelaide, South Australia, Australia

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East Mebourne, Victoria, Australia

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Parkville, Victoria, Australia

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Wein, Austria

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B-Leuven, Belgium

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Brussels, Belgium

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Edegem, Belgium

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Yvoir, Belgium

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Aarhus, Denmark

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Helsinki, Finland

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Lille, France

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Lyon, France

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Nantes, France

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Paris, France

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Pessac, France

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Poitiers, France

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Strasbourg, France

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Hamburg, Germany

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Leipzig, Germany

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Mainz, Germany

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Mannheim, Germany

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Co Galway, Galway, Ireland

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Dublin, Ireland

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Ramat Gan, Israel

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Bari, Italy

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Bologna, Italy

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Milan, Italy

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Napoli, Italy

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Orbassano, Italy

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Roma, Italy

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Nijmegen, Netherlands

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Rotterdam, Netherlands

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Trondheim, Norway

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Lima, Lima Province, Peru

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Singapore, Singapore

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Parktown, Gauteng, South Africa

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Soweto, Gauteng, South Africa

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Kyunggi-Do, South Korea

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Barcelona, Spain

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Madrid, Spain

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Gothenburg, Sweden

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Lund, Sweden

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Stockholm, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Basel, Switzerland

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Glasgow, Central, United Kingdom

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London, Greater London, United Kingdom

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Related Publications (2)

• 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.

  PMID: 17138817 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

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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2005
• First Posted: January 13, 2005
• Study Start: February 1, 2005
• Primary Completion: September 1, 2006
• Study Completion: April 1, 2008
• Last Updated: March 2, 2012
• Results First Posted: February 24, 2010

Record last verified: 2012-02

Locations

CA (3); DE (4); SE (5); US (32); PE (1); ES (2); GB (2); IL (1); IT (6); ZA (2); NO (1); IE (2); FI (1); AU (1); SG (1); FR (7); BE (4); DK (1); NL (2); KR (1); CH (1)