Clinical trial NCT00320190: Study of Dasatinib in Patients With Chronic Phase Chronic Myeloid Leukemia and a Suboptimal Response to Imatinib
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia, Myeloid, Chronic
Keywords: Chronic phase CML, with a suboptimal response after treatment with imatinib
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-05-03
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.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 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

Primary outcomes:
measure: Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)
timeFrame: At 12 months from baseline
Secondary outcomes:
measure: 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
timeFrame: Months 1 to 12, continuously, and Months 12 to 24, continuously
measure: Percentage of Participants With On-study AEs of Special Interest
timeFrame: Months 1 to 12, continuously, and Months 12 to 24, continuously
measure: Median Time to MMolR
timeFrame: At 3, 6, 9, and 12 months from baseline
measure: Percentage of Participants With Complete Cytogenetic Response
timeFrame: At 6 and 12 months from baseline
measure: Median Time to Treatment Failure
timeFrame: Randomization to disease progression, death, or discontinuation (to 12 months)
measure: Median Time to Progression-free Survival
timeFrame: Randomization to disease progression or death (to 12 months)
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Local Institution
city: Charleroi
country: Belgium
facility: Local Institution
city: Helsinki
country: Finland
facility: Local Institution
city: Tampere
country: Finland
facility: Local Institution
city: Lyon Cedex 03
country: France
facility: Local Institution
city: Marseille Cedex 9
country: France
facility: Local Institution
city: Montpellier Cedex 5
country: France
facility: Local Institution
city: Paris Cedex 10
country: France
facility: Local Institution
city: Rennes
country: France
facility: Local Institution
city: Strasbourg Cedex
country: France
facility: Local Institution
city: Toulouse Cedex 09
country: France
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Orbassano (To)
country: Italy
facility: Local Institution
city: Oslo
country: Norway
facility: Local Institution
city: Trondheim
country: Norway
facility: Local Institution
city: Lisboa
country: Portugal
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Saint-Petersburg
country: Russian Federation
facility: Local Institution
city: St.Petersburg
country: Russian Federation
facility: Local Institution
city: Murcia
country: Spain
facility: Local Institution
city: Lund
country: Sweden
facility: Local Institution
city: Orebro
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Glasgow
country: United Kingdom
facility: Local Institution
state: Central
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: London
country: United Kingdom
facility: Local Institution
state: Greater London
city: Leeds
country: United Kingdom
facility: Local Institution
state: North Yorkshire
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: