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

Phase 2

Terminated

Conditions: Leukemia, Myeloid, Chronic

Interventions: Drug: Dasatinib
Drug: Imatinib

Registration Number: NCT00320190

Lead Sponsor: Bristol-Myers Squibb

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 Participants permanently discontinuing treatment before 12 months were considered treatment failures and withdrawn from the study.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 52

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Chronic Phase Chronic Myeloid Leukemia Who Have a Major Molecular Response (MMolR)	At 12 months from baseline	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

Name	Time	Method
Median Time to Progression-free Survival	Randomization to disease progression or death (to 12 months)	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.
Median Time to MMolR	At 3, 6, 9, and 12 months from baseline	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 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	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	Months 1 to 12, continuously, and Months 12 to 24, continuously	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.
Percentage of Participants With Complete Cytogenetic Response	At 6 and 12 months from baseline	Cytogenetic response is based on the prevalence of Ph+ metaphases among cells in metaphase in a bone marrow sample.
Median Time to Treatment Failure	Randomization to disease progression, death, or discontinuation (to 12 months)	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.