The primary purpose of this study was to assess the tolerability of oral asciminib (80 mg QD) in comparison with that of the second generation (2G) Tyrosine Kinase Inhibitor (TKI) nilotinib (300 mg BID), in adult patients with newly diagnosed Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).
Participants were randomized in the study in a 1:1 ratio to asciminib or nilotinib. No crossover of study treatment across arms were allowed. Randomization was stratified based on European Treatment Outcome Study (EUTOS) long-term survival (ELTS) score (low versus intermediate versus high) to help achieve a balance between the treatment arms. The primary analysis was performed when approximately 65 discontinuations of either study treatment due to Adverse Event (AE) occured. Eligible participants on both arms could choose to participate in an optional 2-year Treatment Free Remission (TFR) Phase. Participants with loss of Major Molecular Response (MMR) during TFR Phase were to enter the Treatment Re-initiation (TRI) Phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
568
Rocky Mountain Cancer Centers
Denver, Colorado, United States
Illinois Cancer Care
Peoria, Illinois, United States
Regions Hospital
Saint Paul, Minnesota, United States
Messino Cancer Centers
Asheville, North Carolina, United States
Oncology Hematology Care Inc
Cincinnati, Ohio, United States
Time to discontinuation of study treatment due to adverse event (TTDAE).
TTDAE is defined as the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to adverse event (AE).
Time frame: From date of first dose to date of treatment discontinuation due to AE, assessed up to 5 years
Percentage of participants with Major Molecular response (MMR) at scheduled data collection time points
MMR will be assessed using fusion gene of the BCR and ABL genes (BCR-ABL) transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants with MMR at each time point will be assessed.
Time frame: approximately 7.5 years
Percentage of participants with Major Molecular response (MMR) by scheduled data collection time points
MMR will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants who meet the criteria for having achieved the endpoint (MMR) at or before the specified visit will be calculated.
Time frame: approximately 7.5 years
Percentage of participants with MR4.0 at scheduled data collection time points
MR4.0 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants with MR4.0 at each time point will be assessed.
Time frame: approximately 7.5 years
Percentage of participants with MR4.0 by scheduled data collection time points
MR4.0 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants who meet the criteria for having achieved the endpoint (MR4.0) at or before the specified visit will be calculated
Time frame: approximately 7.5 years
Percentage of participants with MR4.5 at scheduled data collection time points
MR4.5 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants with MR4.5 at each time point will be assessed.
Time frame: approximately 7.5 years
Percentage of participants with MR4.5 by scheduled data collection time points
MR4.5 will be assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. The percentage of participants who meet the criteria for having achieved the endpoint (MR4.5) at or before the specified visit will be calculated
Time frame: approximately 7.5 years
Percentage of participants with Complete Hematological response (CHR) at scheduled data collection time points
Hematologic response will be assessed by complete blood count and physical examination at each visit. The percentage of participants with CHR at each time point will be assessed.
Time frame: approximately 7.5 years
Percentage of participants with Complete Hematological response (CHR) by scheduled data collection time points
Hematologic response will be assessed by complete blood count and physical examination at each visit. The percentage of participants who meet the criteria for having achieved the endpoint (CHR) at or before the specified visit will be calculated
Time frame: approximately 7.5 years
Percentage of participants with BCR::ABL1 ratio ≤1% at scheduled data collection time points
The percentage of participants who meet the criteria for having achieved BCR::ABL1 ratio ≤1% at the specified visit will be calculated
Time frame: approximately 7.5 years
Percentage of participants with BCR::ABL1 ratio ≤1% by scheduled data collection timepoints
The percentage of participants who meet the criteria for having achieved BCR::ABL1 ratio ≤1% at or before the specified visit will be calculated
Time frame: approximately 7.5 years
Duration of MMR
Duration of MMR is defined as the time between the date of the first documented achievement MMR and the earliest date of loss of MMR, treatment failure, progression to AP/BC, or CML-related death.
Time frame: approximately 7.5 years
Duration of MR4.0
Duration of MR4.0 is defined as the time between the date of the first documented achievement MR4 and the earliest date of loss of MR4, treatment failure, progression to AP/BC, or CML-related death
Time frame: approximately 7.5 years
Duration of MR4.5
Duration of MR4.5 is defined as the time between the date of the first documented achievement MR4.5 and the earliest date of loss of MR4.5, treatment failure, progression to AP/BC, or CML-related death.
Time frame: approximately 7.5 years
Time to first MMR
Time to first MMR is defined as the time from the date of randomization to the date of the first documented occurrence of MMR.
Time frame: approximately 7.5 years
Time to first MR4.0
Time to first MR4.0 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.
Time frame: approximately 7.5 years
Time to first MR4.5
Time to first MR4.5 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.5.
Time frame: approximately 7.5 years
Time to treatment failure (TTF).
TTF is defined as the time from date of randomization to the first/earliest documented date of any of the following events: * Treatment failure per European leukemia network (ELN) criteria, * Confirmed loss of MMR (in 2 consecutive tests) at any time while on study treatment, * Discontinuation from study treatment due to any reason
Time frame: approximately 7.5 years
Event free survival (EFS)
EFS is defined as the time from the date of the first dose of study treatment to the earliest occurrence of treatment failure, confirmed lost of MMR, discontinuation due to AE, progression to AP/BC, and death from any cause.
Time frame: approximately 7.5 years
Progression free survival (PFS).
PFS is defined as the time from the date of randomization to the earliest occurrence of progression to AP/BC or death from any cause.
Time frame: approximately 7.5 years
Overall survival (OS).
OS is defined as the time from the date of randomization to the date of death from any cause.
Time frame: approximately 7.5 years
Time to treatment discontinuation (TTD) due to selected reasons
TTD is the time from the date of first dose of study treatment to the date of discontinuation of study treatment due to lack of efficacy, treatment failure, disease progression, suboptimal response or death
Time frame: approximately 7.5 years
Change from baseline in overall scores and individual scales of the European organization for research and treatment of cancer - quality of life questionnaire (EORTC QLQ-C30)
Change from baseline in Overall Scores and individual domains of the EORTC QLQ-C30. The EORTC QLQ-C30 contains 30 items and is composed of both multi-item scales and single-item measures based on the participant's experience over the past week. These include five functional scales (physical, role, emotional, cognitive and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QoL scale.
Time frame: approximately 7.5 years
Change from baseline in overall scores and individual scales of the European organization for research and treatment of cancer CML module (EORTC QLQ-CML24)
Change from baseline in Overall Scores and individual domains of the EORTC QLQ-CML24. The EORTC QLQ-CML24 assesses specific concepts relevant to the experience of patients with CML. The QLQ-CML24 has 24 items which assess symptom burden, impact on daily life and on worry/mood, body image problems, and satisfaction with care and with social life based on the participant's experience over the past week.
Time frame: approximately 7.5 years
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