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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
387
Tablets; oral; 70 mg BID, depending on response
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.
Time frame: 2 years
Number of Imatinib-intolerant Participants With MCyR
Determination of cytogenetic response was based on the prevalence of Ph+ metaphases among cells with metaphases in a bone marrow sample. MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Time frame: Baseline to 2 years
Percentage of Participants Who Achieved MCyR and Did Not Progress at 12 and 24 Months
Based on the Kaplan-Meier estimate of the duration of response. Determination of 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 and Partial Cytogenetic Response (PCyR) - 1% to 35% Ph+ metaphases.
Time frame: 12 and 24 Months
Median Time From First Dosing Date to Date of MCyR
MCyR is the combination of CCyR-0% Ph+ metaphases and PCyR - 1% to 35% Ph+ metaphases.
Time frame: Baseline (within 4 weeks of Day 1) and every 12 weeks
Number of Participants With Complete Hematologic Response (CHR)
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
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Local Institution
Anaheim, California, United States
Local Institution
Loma Linda, California, United States
Local Institution
Los Angeles, California, United States
Local Institution
Stanford, California, United States
Local Institution
Vallejo, California, United States
Local Institution
Hartford, Connecticut, United States
Local Institution
Washington D.C., District of Columbia, United States
Local Institution
Jacksonville, Florida, United States
Local Institution
Tampa, Florida, United States
Local Institution
Atlanta, Georgia, United States
...and 75 more locations
Time frame: 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
Based on the Kaplan-Meier estimate of the duration of response. CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \< 450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Time frame: 12 and 24 months
Median Time From First Dosing Until CHR
CHR=all of the following criteria: white blood cell count ≤ institutional upper limit of normal; platelets \<450,000/mm\^3; no blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; peripheral blood basophils ≤20%; no extramedullary involvement. Response, as defined, must be maintained for at least 4 weeks after first documented. A CHR could begin only 14 days after dosing start date.
Time frame: Baseline (within 72 hours of start of therapy), weekly until Week 12, every 3 months until off-study
Number of Participants With Major Molecular Response (MMR)
MMR is defined as ≤3 log reduction in BCR-ABL levels from the standardized baseline value of BCR-ABL:Control Gene ratio. The international ratio is obtained by multiplying BCR-ABL:Control gene ratio by the lab-specific conversion factor.
Time frame: Baseline to 2 years
Minimal Clinically Significant Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire Scores
Health-related quality of life as measured by FACT-G, which comprises 27 questions in 4 domains: PWB, SWB, EWB, FWB. Total FACT-G score=summation of the 4 subscale scores and ranges from 0 to 108. Higher scores=better health-related quality of life. Total Score change of 7 or more=minimal clinical important change; PWB, EWB, \& FWB score change of 3 or more, and SWB score change of 2 or more=minimal clinical important change. Baseline FACT-G measurements can be found in Baseline Characteristics.
Time frame: Baseline, Day 29, every 4 weeks for the first 24 weeks, then every 12 weeks for the remainder of treatment, after end of treatment. Treatment continued until disease progression or development of toxicity or until other protocol-defined criteria.
Number of Imitanib-intolerant Participants With Drug-related Adverse Events (AEs), Death Within 30 Days of Last Dose, Death, and AEs Leading to Discontinuation, Serious Adverse Events (SAEs), Grade 3-4 Thrombocytopenia, Grade 4-4 Neutropenia, and Any AE
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Time frame: Continuously, from baseline through 2 years
Number of Imitanib-resistant Participants With Drug-related AEs, Death Within 30 Days of Last Dose, Death, AEs Leading to Discontinuation, SAEs, Grade 3-4 Thrombocytopenia, Grade 3-4 Neutropenia, and Any AE
AE=any new untoward medical occurrence or worsening of a preexisting medical condition regardless of causal relationship with treatment. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires or prolongs inpatient hospitalization; results in persistent or significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event. Graded by National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. (1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death)
Time frame: Continuously, from baseline through 2 years
Blood Sample Collection for Pharmacokinetic (PK) Analysis of Dasatinib
Blood samples were collected for PK to be included in separate population PK analyses.
Time frame: Day 8 of study; pretreatment through sample between 30 minutes and 3 hours following treatment, a sample between 5 hours and 8 hours following treatment and a sample at 12 hours, prior to the next dose.