Study of Dasatinib in Patients With Chronic Phase Chronic Myeloid Leukemia and a Suboptimal Response to Imatinib

NCT00320190 | Terminated Phase 2 Results

• 2 other identifiers: CA180-043EUDRACT Number: 2005-005153-22
• Study Type: interventional
• Target: 52
• Locations: 11 countries
• Sites: 27

Brief Summary

The purpose of this study is to compare the efficacy of dasatinib with that of high-dose (800-mg) imatinib in participants with chronic phase chronic myeloid leukemia who achieved only a suboptimal response after at least 3 months of monotherapy with 400-mg imatinib. The safety of these treatments will also be evaluated.

Conditions

Leukemia, Myeloid, Chronic

Keywords

Chronic phase CML, with a suboptimal response after treatment with imatinib

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)

  MMolR is defined as reduction in transcript levels of the breakpoint cluster region (BCR)-V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL) gene of at least 3 log. The BCR-ABL gene has a role in the production of a mutated protein that converts bone marrow stem cells from normal to leukemic.

  At 12 months from baseline

Secondary Outcomes (6)

• Percentage of Participants With Death as Outcome, Adverse Events (AEs), Treatment-related AEs, Serious Adverse Events (SAEs), Treatment-related SAEs, and AEs Leading to Discontinuation

  Months 1 to 12, continuously, and Months 12 to 24, continuously

• Percentage of Participants With On-study AEs of Special Interest

  Months 1 to 12, continuously, and Months 12 to 24, continuously

• Median Time to MMolR

  At 3, 6, 9, and 12 months from baseline

• Percentage of Participants With Complete Cytogenetic Response

  At 6 and 12 months from baseline

• Median Time to Treatment Failure

  Randomization to disease progression, death, or discontinuation (to 12 months)

Study Arms (2)

Dasatinib

ACTIVE COMPARATOR

Participants with chronic phase chronic myeloid leukemia (CML) who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg.

Drug: Dasatinib

Imatinib

ACTIVE COMPARATOR

Participants with chronic phase CML who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg.

Drug: Imatinib

Interventions

Imatinib DRUG

Imatinib tablets administered orally at a dose of 400 mg twice daily. Each 400- mg dose to be taken with a meal and a large glass of water.

Imatinib

Dasatinib DRUG

Dasatinib tablets administered orally at a dose of 100 mg once daily.

Dasatinib

Eligibility Criteria

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

You may qualify if:

• Chronic phase Ph\^+ chronic myeloid leukemia (CML) demonstrating only a suboptimal response, defined as a hematologic response that is less than a complete hematologic response after at least 3 months of monotherapy with imatinib, 400 mg; a cytogenic response (CgR) that is less than a partial CgR (PCgR) after at least 6 months of monotherapy with imatinib, 400 mg; a PCgR after at least 12 months of monotherapy with imatinib, 400 mg; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with imatinib, 400 mg.
• Either gender
• Age of 18 years or older

You may not qualify if:

• Previous diagnosis of accelerated phase or blast crisis CML
• Uncontrolled or significant cardiovascular disease
• History of significant bleeding disorder unrelated to CML
• Concurrent malignancies
• Intolerance of imatinib, 400 mg
• Prior treatment with imatinib at a dose higher than 400 mg
• Prior stem cell transplantation and/or high-dose chemotherapy for CML

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (27)

Local Institution

Antwerp, 2060, Belgium

Location

Local Institution

Charleroi, 6000, Belgium

Location

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Helsinki, 00029, Finland

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Tampere, 33380, Finland

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Lyon, 69437, France

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Marseille, 13273, France

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Montpellier, 34295, France

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Paris, 75475, France

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Rennes, 35033, France

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Strasbourg, 67091, France

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Toulouse, 31059, France

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Leipzig, 04103, Germany

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Orbassano (To), 10043, Italy

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Oslo, 0027, Norway

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Trondheim, 7006, Norway

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Lisbon, 1649-035, Portugal

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Moscow, 125167, Russia

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Saint Petersburg, 191024, Russia

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Saint Petersburg, 197022, Russia

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Murcia, 30008, Spain

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Lund, 221 85, Sweden

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Örebro, 70185, Sweden

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Uppsala, 751 85, Sweden

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Glasgow, Central, G31 2ER, United Kingdom

Location

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London, Greater London, SE5 9RS, United Kingdom

Location

Local Institution

London, Greater London, W12 ONN, United Kingdom

Location

Local Institution

Leeds, North Yorkshire, LS9 7FT, United Kingdom

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase

Interventions

Imatinib Mesylate; 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)

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

Limitations and Caveats

Enrollment terminated prematurely on September 5, 2008, due to slow accrual. Only 32 of 156 planned participants were randomized from August 2, 2006. Per BMS standards, findings were reported in a synopsis format, with only safety results included.

Results Point of Contact

• Title: Bristol-Myers Squibb 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: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2006
• First Posted: May 3, 2006
• Study Start: August 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: October 30, 2013
• Results First Posted: July 7, 2011

Record last verified: 2011-07

Locations

DE (1); FR (7); RU (3); BE (2); FI (2); NO (2); SE (3); PT (1); IT (1); ES (1); GB (4)