A Phase III Study of Dasatinib vs. Imatinib in Patients With Newly Diagnosed Chronic Phase CML (DASISION)
The purpose of this clinical research study is to compare the rate of confirmed complete cytogenetic response (cCCyR) of dasatinib to imatinib therapy within 12 months after randomization in newly diagnosed chronic phase Philadelphia positive chronic myeloid leukemia (Ph+ CML) patients. The safety of this treatment will also be studied.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label, Randomized, Multicenter Phase III Trial of Dasatinib (SPRYCEL®) vs. Standard Dose Imatinib (400 mg) in the Treatment of Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive Chronic Myeloid Leukemia|
- Number of Participants With Best Confirmed Complete Cytogenetic Response (cCCyR) Within 12 Months [ Time Frame: Pre-treatment, every 3 months up to 12 months ] [ Designated as safety issue: No ]Cytogenetic response (CyR) is based on the prevalence of Philadelphia positive (Ph+) cells in metaphase from Bone Marrow (BM) sample. (Ideally, 25 metaphases but at least 20 metaphases from a BM sample were evaluated). Complete Cytogenetic Response (CCyR)=0% Ph+ cells in metaphase in BM. A confirmed cytogenetic response (cCCyR)=those in which all measurements up to at least 28 days after the initial response show an equivalent or better complete cytogenetic response.
- Time-in Confirmed cCCyR at Any Time [ Time Frame: Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint or investigator's decision ] [ Designated as safety issue: No ]Time-in cCCyR at any time was computed for all randomized subjects. For subjects with cCCyR at any time, it is measured from the time measurement criteria are first met for CCyR(provided it is confirmed later) until the date of progression or death. Subjects with cCCyR who neither progress nor die are censored on the date of their last cytogenetic assessment. Subjects without cCCyR are considered to have progressed on day 1.
- Number of Participants With Major Molecular Response (MMR) at Any Time [ Time Frame: Pre-treatment, every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]Molecular response was assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction (RQ-PCR). A major molecular response (MMR) is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (i.e., at least 3 log reduction from a standardized baseline value).
- Time to Confirmed CCyR Overall [ Time Frame: Every 3 months for 2 years, then once per year for 3 years and/ or once per year for subjects in confirmed complete cytogenetic response at any timepoint ] [ Designated as safety issue: No ]
The Time-to cCCyR for participants with cCCyR is defined as the time from the randomization date until criteria are first met for CCyR (provided it is confirmed later). The time-to cCCyR for all randomized subjects censors non-responders who do not progress at their cytogenetic assessments and non-responders who progress at the maximum time of all randomized subjects.
- Time to MMR Overall [ Time Frame: Every 3 months for 2 years, then every 6 months for 3 years ] [ Designated as safety issue: No ]The Time-to MMR for participants with MMR is defined as the time from randomization date until measurement criteria are first met for MMR. The time-to MMR for all randomized subjects censor non-responders who do not progress at their last molecular assessments and non-responders who progress at the maximum time of all randomized subjects.
- Percentage of Participants With Progression-free Survival (PFS) at 12 Months [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: No ]PFS=time from randomization until progression (any progression/death within 30 days of last dosing date, or between 30-60 days of last dosing prior to start of secondary therapy). Those who did not progress/die or who progressed/died after 60 days of last dose were censored at last on-study hematologic/cytogenetic assessment; those with progression/death 30-60 days of last dosing date & after start date of secondary therapy censored at last on-study hematologic/cytogenetic assessment prior to start of secondary therapy; those who had not received study treatment censored on date randomized.
- Percentage of Participants With Overall Survival (OS) at 12 Months [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: No ]Overall survival (OS) was defined as the time from randomization to the date of death. If the participant had not died, survival was censored on last date the participant was known to be alive.
- Number of Participants With Adverse Events (AEs), Drug-related AEs, Drug-related Grade 3/4 AEs, Drug-related Fluid Retention AEs (FRAEs), Drug-related Serious Adverse Events(SAEs), Drug-related AEs Leading to Discontinuation, and All Deaths [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: Yes ]Grade 3=Severe, Grade 4=Life-threatening or disabling. AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- Number of Participants With Grade 3/4 On Study Laboratory Abnormalities [ Time Frame: Participants were followed for at least 5 years ] [ Designated as safety issue: Yes ]Grade 3= Severe AE; Grade 4=Life-threatening or disabling AE. Absolute neutrophil: grade 3 < 1000-500/mm^3; grade 4 < 500/mm^3. Hemoglobin: grade 3 < 8.0-6.5 g/dL; grade 4 < 6.5 g/dL. Platelets: grade 3 < 50,000-25,000/mm^3; grade 4 < 25,000/mm^3. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST): grade 3 >5.0-20 x ULN (upper limit of normal), grade 4 > 20 x ULN. Total Bilirubin: grade 3 > 3-10 x ULN; grade 4 > 10x ULN. Sample normal ranges (may vary by institution): ALT, Female: 7-30 U/L, Male: 10-55 U/L; AST, Female: 9-25 U/L, Male10-40 U/L; Total Bilirubin: total 0.0-1.0 mg/dL
|Study Start Date:||September 2007|
|Estimated Study Completion Date:||December 2015|
|Primary Completion Date:||December 2009 (Final data collection date for primary outcome measure)|
Tablets, oral, dasatinib 50-140 mg once daily (QD)
|Active Comparator: B||
Tablets, oral, imatinib 200-800 mg, QD
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|Study Director:||Bristol-Myers Squibb||Bristol-Myers Squibb|