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

This study has been terminated.
(Terminated due to slow participant accrual)
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00320190
First received: May 1, 2006
Last updated: October 1, 2013
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Leukemia, Myeloid, Chronic
Drug: Imatinib
Drug: Dasatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Randomized Study of Dasatinib vs High-dose (800-mg) Imatinib in the Treatment of Subjects With Chronic Phase Chronic Myeloid Leukemia Who Have Had a Suboptimal Response After at Least 3 Months of Therapy With 400 mg Imatinib

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR) [ Time Frame: At 12 months from baseline ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Months 1 to 12, continuously, and Months 12 to 24, continuously ] [ Designated as safety issue: Yes ]
    AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. SAE=any untoward medical occurrence that at any dose results in death, persistent or significant disability/incapacity, drug dependency, or drug abuse; prolongs inpatient hospitalization; or is life-threatening, a congenital anomaly/birth defect, or an important medical event. Treatment related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

  • Percentage of Participants With On-study AEs of Special Interest [ Time Frame: Months 1 to 12, continuously, and Months 12 to 24, continuously ] [ Designated as safety issue: Yes ]
    GI=gastrointestinal. AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with treatment. Grade 1=mild; Grade 2=moderate; Grade 3=severe and undesirable; Grade 4=life-threatening or disabling; Grade 5=death. Percentages based on the number of participants with a specific grade at baseline. Participants without on-study test values for a particular laboratory analyte are not included in the reporting of that analyte.

  • Median Time to MMolR [ Time Frame: At 3, 6, 9, and 12 months from baseline ] [ Designated as safety issue: No ]
    Time to MMolR is defined as the time from first treatment dose until measurement criteria are first met for MMolR. MMolR is defined as a reduction in transcript levels of the BCR-ABL gene of at least 3 log from baseline.

  • Percentage of Participants With Complete Cytogenetic Response [ Time Frame: At 6 and 12 months from baseline ] [ Designated as safety issue: No ]
    Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.

  • Median Time to Treatment Failure [ Time Frame: Randomization to disease progression, death, or discontinuation (to 12 months) ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as the time in days from randomization to progressive disease documented by the investigator, to death from any cause without prior progression, or to early treatment discontinuation for any reason, whichever occurs first. Participants without disease progression or who do not die and complete the 12-month study treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.

  • Median Time to Progression-free Survival [ Time Frame: Randomization to disease progression or death (to 12 months) ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time in days from randomization to progressive disease documented by the investigator or to death from any cause without prior progression. Participants without progressive disease or who do not die and complete the 12-month treatment are censored on the date of their last molecular, cytogenetic, or hematologic assessment.


Enrollment: 52
Study Start Date: August 2006
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dasatinib
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
Dasatinib tablets administered orally at a dose of 100 mg once daily.
Active Comparator: Imatinib
Participants with chronic phase CML who had only a suboptimal response after at least 3 months of therapy with imatinib, 400 mg.
Drug: Imatinib
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.

Detailed Description:

Participants were randomized 2:1 to dasatinib or high-dose imatinib, respectively. Randomization was stratified by a suboptimal response, defined as a hematologic response less than a complete hematologic response after at least 3 months of monotherapy with 400-mg imatinib; a cytogenic response (CgR) less than a partial CgR (PCgR) after at least 6 months of monotherapy with 400-mg; a PCgR after at least 12 months of monotherapy with 400-mg imatinib; or less than a major molecular response with a complete CgR after at least 18 months of monotherapy with 400-mg imatinib.

Participants received either dasatinib or imatinib for 12 months or until disease progression, unacceptable toxicity, consent withdrawal, or study discontinuation. After 12 months, who had a confirmed major molecular response and were still receiving dasatinib, 100 mg, or imatinib, 800 mg, were eligible to extend treatment for an additional 12 months. Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320190

Locations
Belgium
Local Institution
Antwerpen, Belgium, 2060
Local Institution
Charleroi, Belgium, 6000
Finland
Local Institution
Helsinki, Finland, 00029
Local Institution
Tampere, Finland, 33380
France
Local Institution
Lyon Cedex 03, France, 69437
Local Institution
Marseille Cedex 9, France, 13273
Local Institution
Montpellier Cedex 5, France, 34295
Local Institution
Paris Cedex 10, France, 75475
Local Institution
Rennes, France, 35033
Local Institution
Strasbourg Cedex, France, 67091
Local Institution
Toulouse Cedex 09, France, 31059
Germany
Local Institution
Leipzig, Germany, 04103
Italy
Local Institution
Orbassano (To), Italy, 10043
Norway
Local Institution
Oslo, Norway, 0027
Local Institution
Trondheim, Norway, 7006
Portugal
Local Institution
Lisboa, Portugal, 1649-035
Russian Federation
Local Institution
Moscow, Russian Federation, 125167
Local Institution
Saint-Petersburg, Russian Federation, 191024
Local Institution
St.Petersburg, Russian Federation, 197022
Spain
Local Institution
Murcia, Spain, 30008
Sweden
Local Institution
Lund, Sweden, 221 85
Local Institution
Orebro, Sweden, 70185
Local Institution
Uppsala, Sweden, 751 85
United Kingdom
Local Institution
Glasgow, Central, United Kingdom, G31 2ER
Local Institution
London, Greater London, United Kingdom, W12 ONN
Local Institution
London, Greater London, United Kingdom, SE5 9RS
Local Institution
Leeds, North Yorkshire, United Kingdom, LS9 7FT
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00320190     History of Changes
Other Study ID Numbers: CA180-043, EUDRACT Number: 2005-005153-22
Study First Received: May 1, 2006
Results First Received: June 6, 2011
Last Updated: October 1, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Bristol-Myers Squibb:
Chronic phase CML, with a suboptimal response after treatment with imatinib

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Imatinib
Dasatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014