Clinical Trials List
Protocol NumberCABL001E2201
NCT Number(ClinicalTrials.gov Identfier)NCT03578367
Completed
2018-11-22 - 2021-10-26
Phase II
Recruiting3
ICD-10C92.10
Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission
A Phase 2, Multi-center, Open-label, Randomized Study of Oral Asciminib Added to Imatinib Versus Continued Imatinib Versus Switch to Nilotinib in Patients With CML-CP Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response
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Trial Applicant
NOVARTIS (TAIWAN) CO., LTD.
-
Sponsor
Novartis Pharmaceuticals
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Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- 高小雯 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Luh Tang Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
- 徐思淳 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Chronic myeloid leukemia(CML)
Objectives
The primary objective of this study is to assess whether asciminib 40 mg once daily (QD) + imatinib 400 mg QD or asciminib 60 mg QD + imatinib 400 mg QD is more effective than continued imatinib by testing the MR rate at 48 weeks.
Test Drug
ABL001, GLIVEC (STI571), Tasigna (AMN107)
Active Ingredient
ABL001 (Asciminib)
AMN107 (Nilotinib)
STI571 (Imatinib)
AMN107 (Nilotinib)
STI571 (Imatinib)
Dosage Form
Film-Coated tablet
Film-Coated tablet
Hard capsule
Film-Coated tablet
Hard capsule
Dosage
20mg, 40mg
100mg, 400mg
150 mg, 200 mg
100mg, 400mg
150 mg, 200 mg
Endpoints
Primary Outcome Measures :
Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone [ Time Frame: at 48 weeks ]
Proportion of subjects still treated with the randomized treatment at 48 weeks and are in MR4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all subjects randomized to the respective treatment arm.
Secondary Outcome Measures :
MR^4.5 rate at 48 weeks [ Time Frame: at 48 weeks ]
Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Rate of MR^4.5 at 96 weeks [ Time Frame: at 96 weeks ]
Proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks
Rate of MR^4.5 by 48 and 96 weeks [ Time Frame: by 48 weeks and 96 weeks ]
Best observed rate of MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point
Sustained MR^4.5 from 48 weeks until 96 weeks [ Time Frame: from 48 weeks until 96 weeks ]
Percentage of participants who are in MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at both 48 and 96 weeks and who have no loss of MR^4.5 in between those two time points. This endpoint will be analyzed at 96 weeks.
Time to MR^4.5 [ Time Frame: up to 96 weeks ]
Time to MR^4.5 is the time from randomization to first MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR^4.5
Difference in rate of MR^4.5 at 48 weeks [ Time Frame: at 48 weeks ]
Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax [ Time Frame: up to Week 4 Day 28 ]
The maximum (peak) observed drug concentration after dose administration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax [ Time Frame: up to Week 4 Day 28 ]
The time to reach maximum (peak) drug concentration after dose administration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin [ Time Frame: up to 96 weeks ]
Minimum drug concentration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast [ Time Frame: up to Week 4 Day 28 ]
The AUC from time zero to the last measurable concentration sampling time (Tlast)
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau [ Time Frame: up to Week 4 Day 28 ]
The AUC calculated to the end of a dosing interval (tau) at steady-state
Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone [ Time Frame: at 48 weeks ]
Proportion of subjects still treated with the randomized treatment at 48 weeks and are in MR4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all subjects randomized to the respective treatment arm.
Secondary Outcome Measures :
MR^4.5 rate at 48 weeks [ Time Frame: at 48 weeks ]
Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Rate of MR^4.5 at 96 weeks [ Time Frame: at 96 weeks ]
Proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 96 weeks
Rate of MR^4.5 by 48 and 96 weeks [ Time Frame: by 48 weeks and 96 weeks ]
Best observed rate of MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) under randomized treatment up to the specific time point
Sustained MR^4.5 from 48 weeks until 96 weeks [ Time Frame: from 48 weeks until 96 weeks ]
Percentage of participants who are in MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at both 48 and 96 weeks and who have no loss of MR^4.5 in between those two time points. This endpoint will be analyzed at 96 weeks.
Time to MR^4.5 [ Time Frame: up to 96 weeks ]
Time to MR^4.5 is the time from randomization to first MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) computed only for subjects who achieved MR^4.5
Difference in rate of MR^4.5 at 48 weeks [ Time Frame: at 48 weeks ]
Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 ratio of ≤ 0.0032%) at 48 weeks between asciminib+imatinib and nilotinib
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax [ Time Frame: up to Week 4 Day 28 ]
The maximum (peak) observed drug concentration after dose administration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax [ Time Frame: up to Week 4 Day 28 ]
The time to reach maximum (peak) drug concentration after dose administration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin [ Time Frame: up to 96 weeks ]
Minimum drug concentration
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast [ Time Frame: up to Week 4 Day 28 ]
The AUC from time zero to the last measurable concentration sampling time (Tlast)
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau [ Time Frame: up to Week 4 Day 28 ]
The AUC calculated to the end of a dosing interval (tau) at steady-state
Inclution Criteria
Key Inclusion criteria
1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female patients ≥ 20 years of age with a confirmed diagnosis of CMLCP.
3. Minimum of two years (24 calendar months) treatment with imatinib first line
for CML-CP (patients have to be on imatinib 400mg QD at randomization and
had no dose change in the past 3 months).
4. BCR-ABL1 levels > 0.01% IS and ≤ 1% IS at the time of study entry as
confirmed with a central assessment at screening; patients must not have
achieved deep molecular response (MR4 IS) at any time during prior imatinib
treatment.
5. Patient must meet the following laboratory values before randomization:
● Absolute Neutrophil Count ≥ 1.5 x 109 L
● Platelets ≥ 75 x 109/L
● Hemoglobin ≥ 9 g/dL
● Serum creatinine (sCr) < 1.5 mg/dL
● Total bilirubin (TBL) ≤ 1.5 x upper limit of normal (ULN) except for patients
with Gilbert’s syndrome who may only be included with total bilirubin ≤ 3.0 x
ULN
● Aspartate aminotransaminase (AST) ≤ 3.0 x ULN
● Alanine aminotransaminase (ALT) ≤ 3.0 x ULN
● Alkaline phosphatase (ALP) ≤ 2.5 x ULN
6. Patients must have the following laboratory values (≥ lower limit of normal
(LLN)) or corrected to within normal limits with supplements prior to
randomization: potassium, magnesium, phosphorus, total calcium (corrected for
serum albumin).
1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female patients ≥ 20 years of age with a confirmed diagnosis of CMLCP.
3. Minimum of two years (24 calendar months) treatment with imatinib first line
for CML-CP (patients have to be on imatinib 400mg QD at randomization and
had no dose change in the past 3 months).
4. BCR-ABL1 levels > 0.01% IS and ≤ 1% IS at the time of study entry as
confirmed with a central assessment at screening; patients must not have
achieved deep molecular response (MR4 IS) at any time during prior imatinib
treatment.
5. Patient must meet the following laboratory values before randomization:
● Absolute Neutrophil Count ≥ 1.5 x 109 L
● Platelets ≥ 75 x 109/L
● Hemoglobin ≥ 9 g/dL
● Serum creatinine (sCr) < 1.5 mg/dL
● Total bilirubin (TBL) ≤ 1.5 x upper limit of normal (ULN) except for patients
with Gilbert’s syndrome who may only be included with total bilirubin ≤ 3.0 x
ULN
● Aspartate aminotransaminase (AST) ≤ 3.0 x ULN
● Alanine aminotransaminase (ALT) ≤ 3.0 x ULN
● Alkaline phosphatase (ALP) ≤ 2.5 x ULN
6. Patients must have the following laboratory values (≥ lower limit of normal
(LLN)) or corrected to within normal limits with supplements prior to
randomization: potassium, magnesium, phosphorus, total calcium (corrected for
serum albumin).
Exclusion Criteria
Key Exclusion criteria
1. Treatment failure according to ELN 2013 criteria during imatinib treatment.
2. Known second chronic phase of CML after previous progression to
accelerated phase/blast crisis (AP/BC).
3. Previous treatment with any TKIs other than imatinib
4. History or current diagnosis of ECG abnormalities indicating significant risk or
safety for subjects participating in the study such as:
● History of myocardial infarction (MI), angina pectoris, coronary artery
bypass graft (CABG) within 6 months prior to randomization
● Concomitant clinically significant arrhythmias, e.g. sustained ventricular
tachycardia, and clinically significant second or third degree atrioventricular
(AV) block without a pacemaker
● Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to
randomization
● 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 including uncorrected hypokalemia
or hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
● Concomitant medications with a "known" risk of Torsades de Pointes per
qtdrugs.org that cannot be discontinued or replaced by safe alternative
medication
● inability to determine the QTcF interval
5. 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 clinically significant hyperlipidemia and high serum
amylase).
6. History of acute pancreatitis within 1 year prior to randomization or past
medical history of chronic pancreatitis or history of acute or chronic liver disease.
7. History of other active malignancy within 3 years prior to randomization with
the exception of basal cell skin cancer, indolent prostate cancer and carcinoma
in situ treated curatively.
1. Treatment failure according to ELN 2013 criteria during imatinib treatment.
2. Known second chronic phase of CML after previous progression to
accelerated phase/blast crisis (AP/BC).
3. Previous treatment with any TKIs other than imatinib
4. History or current diagnosis of ECG abnormalities indicating significant risk or
safety for subjects participating in the study such as:
● History of myocardial infarction (MI), angina pectoris, coronary artery
bypass graft (CABG) within 6 months prior to randomization
● Concomitant clinically significant arrhythmias, e.g. sustained ventricular
tachycardia, and clinically significant second or third degree atrioventricular
(AV) block without a pacemaker
● Resting QTcF ≥ 450 msec (male) or ≥ 460 msec (female) prior to
randomization
● 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 including uncorrected hypokalemia
or hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
● Concomitant medications with a "known" risk of Torsades de Pointes per
qtdrugs.org that cannot be discontinued or replaced by safe alternative
medication
● inability to determine the QTcF interval
5. 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 clinically significant hyperlipidemia and high serum
amylase).
6. History of acute pancreatitis within 1 year prior to randomization or past
medical history of chronic pancreatitis or history of acute or chronic liver disease.
7. History of other active malignancy within 3 years prior to randomization with
the exception of basal cell skin cancer, indolent prostate cancer and carcinoma
in situ treated curatively.
The Estimated Number of Participants
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Taiwan
10 participants
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Global
120 participants
