June 8, 2021
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July 21, 2021
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May 3, 2024
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October 6, 2021
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November 28, 2023 (Final data collection date for primary outcome measure)
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Major Molecular Response (MMR) at week 48 [ Time Frame: at 48 weeks (48 weeks after last patient first dose) ] Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
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Same as current
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- Major Molecular response at week 96 [ Time Frame: at 96 weeks (96 weeks after last patient first dose) ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- Time to discontinuation of study treatment due to Adverse Events (TTDAE) [ Time Frame: 96 weeks after last patient first dose ]
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). For patients ongoing without study treatment discontinuation, on or prior to the analysis cut-off date, the time will be censored at the at the analysis cut-off date.
- Major Molecular response at scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- Major Molecular response by scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- MR4.0 at scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).
- MR4.5 at all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).
- MR4.0 by scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).
- MR4.5 by all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).
- Complete Hematological response (CHR) at all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Hematologic response will be assessed by CBC and physical examination at each visit.
Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:
white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver
- Complete Hematological response (CHR) by all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Hematologic response will be assessed by CBC and physical examination at each visit.
Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:
white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver
- Complete Cytogenic response (CCyR) at Week 48 & Week 96 [ Time Frame: at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose) ]
The CCyR response status will be based on bone marrow assessment, in any patients who have this done due to a clinical indication
- Complete Cytogenic response (CCyR) by Week 48 & Week 96 [ Time Frame: at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose) ]
The CCyR response status will be based on bone marrow assessment, in any patients who have this done due to a clinical indication
- Duration of MMR [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MMR is defined as the time between the date of the first documented achievement of MMR and the earliest date of loss of MMR, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Duration of MR4.0 [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MR4.0 is defined as the time between the date of the first documented achievement of MR4.0 and the earliest date of loss of MR4.0, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Duration of MR4.5 [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MR4.5 is defined as the time between the date of the first documented achievement of MR4.5 and the earliest date of loss of MR4.5, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Time to first MMR [ Time Frame: Planned total follow-up duration of 5 years ]
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 will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MMR.
- Time to first MR4.0 [ Time Frame: Planned total follow-up duration of 5 years ]
Time to first MR4.0 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.0. Time will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.0.
- Time to first MR4.5 [ Time Frame: Planned total follow-up duration of 5 years ]
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 will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.5.
- BCR-ABL1≤1% at scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.
- BCR-ABL1≤1% by scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction.
- Time to treatment failure (TTF) [ Time Frame: Planned total follow-up duration of 5 years ]
TTF is defined as the time from date of randomization to the first/earliest documented date of any of the following events: treatment failure as per ELN, Confirmed loss of MMR while on study treatment, discontinuation from study treatment due to any reason
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the last study assessment date while on treatment, or the EOT (whichever comes first) .
- Failure Free Survival (FFS) [ Time Frame: Planned total follow-up duration of 5 years ]
FFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure per ELN, confirmed loss of MMR, progression to AP/BC, death from any cause.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Event Free Survival (EFS) [ Time Frame: Planned total follow-up duration of 5 years ]
EFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure as per ELN, confirmed loss of MMR ,discontinuation of study treatment due to AE, progression to AP/BC, death from any cause.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Progression Free Survival (PFS) [ Time Frame: Planned total follow-up duration of 5 years ]
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.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Overall Survival (OS) [ Time Frame: Planned total follow-up duration of 5 years ]
OS is defined as the time from the date of randomization to the date of death from any cause. For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last contact before the cut-off date.
- Trough plasma concentrations. [ Time Frame: 48 weeks after last patient first dose ]
Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered.
- Pharmacokinetics (PK) of Asciminib: Cmax [ Time Frame: 48 weeks after last patient first dose ]
Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1).
- PK of Asciminib: Tmax [ Time Frame: 48 weeks after last patient first dose ]
Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time)
- PK of Asciminib: AUCtau and AUClast [ Time Frame: 48 weeks after last patient first dose ]
AUCtau is the area under the plasma concentration-time curve over the dosing interval. AUClast is the area under the plasma concentration-time curve from time zero (time of dose administration) to time of last measurable concentration (mass x time x volume-1)
- PK of Asciminib: CL/F [ Time Frame: 48 weeks after last patient first dose ]
CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1).
- Change from baseline in overall scores and individual scales of the EORTC QLQ-C30 [ Time Frame: baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose ]
The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) consists of functioning scales, symptoms' scales, single-item scales and the global health status quality of life (QoL) scale. A high score for functional and QoL items/scales from the QLQ-30 represents better function and QOL. A high score in symptoms items from QLQ-30 represents worse symptoms.
- Change from baseline in overall scores and individual scales of the EORTC QLQ-CML24 [ Time Frame: baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose ]
The QLQ-CML24 consists of (i) 22 multi-scale items: impact on daily life, symptom burden, impact on worry/mood, satisfaction with care and information, (ii) 2 single items: body image problems, and satisfaction with social life.
A higher score on most of the item scales in QLQ-CML24 reflects a larger impairment in the corresponding domain, with the exception of the satisfaction with care and information, and problems and satisfaction with social life, where a higher score reflects a higher level of satisfaction.
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- Major Molecular response at week 96 [ Time Frame: at 96 weeks (96 weeks after last patient first dose) ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- Time to discontinuation of study treatment due to Adverse Events (TTDAE) [ Time Frame: 96 weeks after last patient first dose ]
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). For patients ongoing without study treatment discontinuation, on or prior to the analysis cut-off date, the time will be censored at the at the analysis cut-off date.
- Major Molecular response at scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- Major Molecular response by scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MMR is defined as a ratio BCR-ABL/ABL ≤0.1% on the international scale (ie, at least 3 log reduction from a standardized baseline value).
- MR4.0 at scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).
- MR4.5 at all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).
- MR4.0 by scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.0 is defined as a ratio BCR-ABL/ABL ≤0.01% on the international scale (ie, at least 4 log reduction from a standardized baseline value).
- MR4.5 by all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Molecular response is assessed using BCR-ABL transcript levels measured by realtime quantitative polymerase chain reaction. MR4.5 is defined as a ratio BCR-ABL/ABL ≤0.0032% on the international scale (ie, at least 4.5 log reduction from a standardized baseline value).
- Complete Hematological response (CHR) at all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Hematologic response will be assessed by CBC and physical examination at each visit.
Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:
white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver
- Complete Hematological response (CHR) by all scheduled data collection time points [ Time Frame: Planned total follow-up duration of 5 years ]
Hematologic response will be assessed by CBC and physical examination at each visit.
Complete Hematological Response (CHR) will be defined as all of the following present for ≥ 4 weeks:
white blood cell(s) (WBC) count < 10 x 10^9/L PLT count < 450 x 10^9/L Basophils < 5% No blasts and promyelocytes in peripheral blood Myelocytes + metamyelocytes < 5% in peripheral blood No evidence of extramedullary disease, including spleen and liver
- Complete Cytogenic response (CCyR) at Week 48 & Week 96 [ Time Frame: at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose) ]
The CCyR response status will be based on the BCR-ABL1 levels measured in peripheral blood by realtime PCR. A BCR-ABL1 (IS) level of <1% is considered equivalent to CCyR
- Complete Cytogenic response (CCyR) by Week 48 & Week 96 [ Time Frame: at 48 weeks and at 96 weeks (48 weeks and 96 weeks after last patient first dose) ]
The CCyR response status will be based on the BCR-ABL1 levels measured in peripheral blood by realtime PCR. A BCR-ABL1 (IS) level of <1% is considered equivalent to CCyR
- Duration of MMR [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MMR is defined as the time between the date of the first documented achievement of MMR and the earliest date of loss of MMR, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Duration of MR4.0 [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MR4.0 is defined as the time between the date of the first documented achievement of MR4.0 and the earliest date of loss of MR4.0, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Duration of MR4.5 [ Time Frame: Planned total follow-up duration of 5 years ]
Duration of MR4.5 is defined as the time between the date of the first documented achievement of MR4.5 and the earliest date of loss of MR4.5, treatment failure, progression to Accelerated Phase/Blast Crisis, or CML-related death
- Time to first MMR [ Time Frame: Planned total follow-up duration of 5 years ]
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 will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MMR.
- Time to first MR4.0 [ Time Frame: Planned total follow-up duration of 5 years ]
Time to first MR4.0 is defined as the time from the date of randomization to the date of the first documented occurrence of MR4.0. Time will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.0.
- Time to first MR4.5 [ Time Frame: Planned total follow-up duration of 5 years ]
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 will be censored at the last molecular assessment date while on treatment, or the End Of Treatment (whichever comes first) for patients who have not experienced MR4.5.
- Time to treatment failure (TTF) [ Time Frame: Planned total follow-up duration of 5 years ]
TTF is defined as the time from date of randomization to the first/earliest documented date of any of the following events: treatment failure as per ELN, Confirmed loss of MMR while on study treatment, discontinuation from study treatment due to any reason
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the last study assessment date while on treatment, or the EOT (whichever comes first) .
- Failure Free Survival (FFS) [ Time Frame: Planned total follow-up duration of 5 years ]
FFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure per ELN, confirmed loss of MMR, progression to AP/BC, death from any cause.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Event Free Survival (EFS) [ Time Frame: Planned total follow-up duration of 5 years ]
EFS is defined as the time from the date of randomization to the earliest occurrence of the following events: treatment failure as per ELN, confirmed loss of MMR ,discontinuation of study treatment due to AE, progression to AP/BC, death from any cause.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Progression Free Survival (PFS) [ Time Frame: Planned total follow-up duration of 5 years ]
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.
For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last study treatment assessment or last post-treatment follow-up.
- Overall Survival (OS) [ Time Frame: Planned total follow-up duration of 5 years ]
OS is defined as the time from the date of randomization to the date of death from any cause. For patients that have not experienced an event prior to or at the analysis cut-off date, the time will be censored at the date of last contact before the cut-off date.
- Trough plasma concentrations. [ Time Frame: 48 weeks after last patient first dose ]
Trough plasma concentration will measure the concentration of asciminib in the blood immediately before the next dose is administered.
- Pharmacokinetics (PK) of Asciminib: Cmax [ Time Frame: 48 weeks after last patient first dose ]
Cmax is the maximum serum concentration of asciminib during a dosing interval (mass x volume-1).
- PK of Asciminib: Tmax [ Time Frame: 48 weeks after last patient first dose ]
Tmax is the time to reach maximum (peak) plasma drug concentration after dose administration (time)
- PK of Asciminib: AUCtau and AUClast [ Time Frame: 48 weeks after last patient first dose ]
AUCtau is the area under the plasma concentration-time curve over the dosing interval. AUClast is the area under the plasma concentration-time curve from time zero (time of dose administration) to time of last measurable concentration (mass x time x volume-1)
- PK of Asciminib: CL/F [ Time Frame: 48 weeks after last patient first dose ]
CL/F is the apparent total body clearance of asciminib from plasma after oral administration (volume x time-1).
- Change from baseline in overall scores and individual scales of the EORTC QLQ-C30 [ Time Frame: baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose ]
The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30) consists of functioning scales, symptoms' scales, single-item scales and the global health status quality of life (QoL) scale. A high score for functional and QoL items/scales from the QLQ-30 represents better function and QOL. A high score in symptoms items from QLQ-30 represents worse symptoms.
- Change from baseline in overall scores and individual scales of the EORTC QLQ-CML24 [ Time Frame: baseline, 48 weeks after last patient first dose, 96 weeks after last patient first dose ]
The QLQ-CML24 consists of (i) 22 multi-scale items: impact on daily life, symptom burden, impact on worry/mood, satisfaction with care and information, (ii) 2 single items: body image problems, and satisfaction with social life.
A higher score on most of the item scales in QLQ-CML24 reflects a larger impairment in the corresponding domain, with the exception of the satisfaction with care and information, and problems and satisfaction with social life, where a higher score reflects a higher level of satisfaction.
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Not Provided
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Not Provided
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A Study of Oral Asciminib Versus Other TKIs in Adult Patients With Newly Diagnosed Ph+ CML-CP
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A Phase III, Multi-center, Open-label, Randomized Study of Oral Asciminib Versus Investigator Selected TKI in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase
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The study is designed to compare the efficacy of asciminib 80 mg QD versus Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the following treatment options for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.
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This study is a phase III, multi-center, open-label, randomized study of oral asciminib 80 mg QD versus Investigator selected TKI (imatinib, nilotinib, dasatinib, or bosutinib) in adult patients with newly diagnosed Ph+ CML-CP. All comparator TKIs will be made available, unless not permitted by local regulations or local Health Authority, or not approved for the treatment of CML in the country.
The study is designed to compare the efficacy of asciminib 80 mg QD with Investigator selected TKI for the treatment of newly diagnosed, previously untreated patients with Ph+ CML-CP. The Investigator selected TKI will be one of the treatment options approved by major Health Authorities for first-line treatment of CML-CP - imatinib 400 mg QD or nilotinib 300 mg BID or dasatinib 100 mg QD or bosutinib 400 mg QD.
Approximately 402 patients will be randomized in a 1:1 ratio to asciminib and Investigator selected TKI.
Randomization will be stratified based on the following two stratification factors:
- ELTS score (low versus intermediate versus high)
- Pre-randomization selected TKI (imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib)).
Prior to randomization, the Investigator, in consultation with the patient, considering the current treatment paradigm and patient characteristics and comorbidities, will make a selection of preference for imatinib or 2G TKI (nilotinib or dasatinib or bosutinib) if the patient is randomized to the comparator arm.
To further ensure that the distribution of patients, between imatinib and 2G TKIs (nilotinib or dasatinib or bosutinib), in the Investigator selected TKI arm is reflective of the use of these agents in clinical practice, the enrollment into the strata of imatinib versus 2G TKI (nilotinib or dasatinib or bosutinib) based on the pre-randomization selection of TKI will be managed by Interactive Response Technology to be approximately 50% versus 50%.
Treatment arms: The study will have 2 treatment arms:
- Arm 1: asciminib 80 mg QD under fasting conditions
- Arm 2: Investigator selected TKI that will include one of the below treatments:
- Imatinib 400 mg QD administered with food
- Nilotinib 300 mg BID administered under fasting conditions
- Dasatinib 100 mg QD administered with or without meal
- Bosutinib 400 mg QD administered with food.
No crossover of study treatment across arms and no change of study treatment within the Investigator selected TKI will be allowed.
Duration of Study treatment: Patients on the study will continue to receive the assigned treatment until the End of Study, or until premature discontinuation due to treatment failure, disease progression or intolerance or due to Investigator or participant decision.
Duration of study: The End of Study will occur 5 years from the last patient first treatment in the study. Patients who discontinue study treatment prematurely due to any reason, will be followed up for survival and progression (to AP/BC) until the End of Study.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Chronic Myeloid Leukemia (CML) Philadelphia Chromosome Positive
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- Drug: Imatinib
Comes in 100 mg and 400 mg tablets and taken orally
Other Name: STI571
- Drug: Nilotinib
Comes in 150 mg capsules and taken orally
Other Name: AMN107
- Drug: Bosutinib
Comes in 100 mg and 400 mg tablets and taken orally
- Drug: Dasatinib
Comes in 70 mg and 100 mg tablets and taken orally
- Drug: Asciminib
Comes in 40 mg tablets and taken orally
Other Name: ABL001
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Not Provided
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Active, not recruiting
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404
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402
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January 18, 2028
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November 28, 2023 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
Exclusion Criteria:
- Previous treatment of CML with any other anticancer agents including chemotherapy and/or biologic agents or prior stem cell transplant, with the exception of hydroxyurea and/or anagrelide. Treatment with either imatinib, or nilotinib, or dasatinib or bosutinib for ≤2 weeks is allowed, but no other treatment with other tyrosine kinase inhibitors prior to randomization is permitted.
- Known cytopathologically confirmed CNS infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
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Impaired cardiac function or cardiac repolarization abnormality including but not limited to any one of the following:
- History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
- Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- QTc ≥ 450 ms (male patients), ≥460 ms (female patients) on the average of three serial baseline ECG (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc.
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
- Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
- Concomitant medication(s) with a "Known risk of Torsades de Pointes" per www.crediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.•Inability to determine the QTcF interval
- Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection; uncontrolled arterial or pulmonary hypertension, uncontrolled clinically significant hyperlipidemia). Please refer to Section 6.3.1
- History of significant congenital or acquired bleeding disorder unrelated to cancer.
- Major surgery within 4 weeks prior to study entry or who have not recovered from prior surgery.
- History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
- History of acute pancreatitis within 1 year prior to randomization or medical history of chronic pancreatitis.
- History of chronic liver disease leading to severe hepatic impairment, or ongoing acute liver disease.
Other protocol-defined Inclusion/exclusion criteria will apply.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Contact information is only displayed when the study is recruiting subjects
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Australia, Austria, Belgium, Bulgaria, Canada, China, Czechia, Denmark, Finland, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Norway, Portugal, Singapore, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
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Russian Federation
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NCT04971226
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CABL001J12301 2021-000678-27 ( EudraCT Number )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
Yes |
Plan Description: |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com |
URL: |
https://www.clinicalstudydatarequest.com |
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Novartis ( Novartis Pharmaceuticals )
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Same as current
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Novartis Pharmaceuticals
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Same as current
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Not Provided
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Study Director: |
Novartis Pharmaceuticals |
Novartis Pharmaceuticals |
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Novartis
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May 2024
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