Clinical Trials List
Protocol NumberCABL001E2201
NCT Number(ClinicalTrials.gov Identfier)NCT03578367
Completed
2018-11-22 - 2021-10-26
Phase II
Recruiting3
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.
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Sponsor
NOVARTIS (TAIWAN) CO., LTD.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/09/15
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- Jih-Luh Tang Division of Hematology & Oncology
- Shang-Ju Wu Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- 林建廷 Division of Hematology & Oncology
- 徐思淳 Division of Hematology & Oncology
- - - Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Lee-Yung Shin
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- Hsiao-Wen Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
CML Chronic Myelogenous Leukemia Leukemia, Myeloid Chronic Hematologic Diseases
Objectives
To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP). An asciminib single agent arm (80 mg daily) was added after the primary analysis to evaluate if asciminib alone could lead to MR4.5 patients in Imatinib for at least one year who have never achieved deep molecular response (DMR).
Test Drug
ABL001, GLIVEC (STI571), Tasigna (AMN107)
Active Ingredient
ABL001 (Asciminib)
ABL001 (Asciminib)
STI571 (Imatinib)
STI571 (Imatinib)
AMN107 (Nilotinib)
AMN107 (Nilotinib)
ABL001 (Asciminib)
STI571 (Imatinib)
STI571 (Imatinib)
AMN107 (Nilotinib)
AMN107 (Nilotinib)
Dosage Form
Tablet
Dosage
20mg
40 mg
100mg
400 mg
150 mg
200 mg
40 mg
100mg
400 mg
150 mg
200 mg
Endpoints
Molecular Response (MR)^4.5 Rate at 48 Weeks and Difference in Rate Between Asciminib + Imatinib and Imatinib Alone Percentage of participants still treated with the randomized treatment at 48 weeks and are in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all participants in the asciminib add-on arms vs imatinib arm. at Week 48
Inclution Criteria
Male or female patients ≥ 18 years of age with a confirmed diagnosis of CML-CP.
Minimum of one year (12 calendar months) treatment with imatinib first line for CML-CP (patients have to be on imatinib 400 mg QD at randomization and had no dose change in the past three months).
For Korea only:
(i) a minimum of one year (12 calendar months) of prior treatment with imatinib for patients with BCR::ABL1 levels > 0.1%, ≤ 1% IS at the time of randomization.
(ii) a minimum of two years (24 calendar months) of prior treatment with imatinib for patients with BCR::ABL 1 levels > 0.01%, ≤ 0.1% IS at the time of randomization.
BCR::ABL1 levels > 0.01% IS (International Scale) and ≤ 1% IS at the time of randomization as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (MR4 IS) confirmed by 2 consecutive tests at any time during prior imatinib treatment. An isolated, single test result with BCR::ABL1 levels < 0.01 % (MR4 IS) is allowed, however, it should not have been observed within the 9 months prior to randomization
Patient must meet the following laboratory values before randomization:
Absolute Neutrophil Count ≥ 1.5 x 10E9/L
Platelets ≥ 75 x 10E9/L
Hemoglobin ≥ 9 g/dL
Serum creatinine < 1.5 mg/dL
Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal) except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN
Aspartate transaminase (AST) ≤ 3.0 x ULN
Alanine transaminase (ALT) ≤ 3.0 x ULN
Alkaline phosphatase ≤ 2.5 x ULN
Serum lipase ≤ 1.5 x ULN
Participants must have the following laboratory values ≥ Lower Limit of Normal or corrected to within normal limits with supplements prior to randomization: potassium increase of up to 6.0 mmol/L is acceptable if associated with creatinine clearance within normal limits ; calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with creatinine clearance* within normal limits) ; magnesium increase up to 3.0 mg/dL or 1.23 mmol/L if associated with creatinine clearance within normal limits.
Minimum of one year (12 calendar months) treatment with imatinib first line for CML-CP (patients have to be on imatinib 400 mg QD at randomization and had no dose change in the past three months).
For Korea only:
(i) a minimum of one year (12 calendar months) of prior treatment with imatinib for patients with BCR::ABL1 levels > 0.1%, ≤ 1% IS at the time of randomization.
(ii) a minimum of two years (24 calendar months) of prior treatment with imatinib for patients with BCR::ABL 1 levels > 0.01%, ≤ 0.1% IS at the time of randomization.
BCR::ABL1 levels > 0.01% IS (International Scale) and ≤ 1% IS at the time of randomization as confirmed with a central assessment at screening; patients must not have achieved deep molecular response (MR4 IS) confirmed by 2 consecutive tests at any time during prior imatinib treatment. An isolated, single test result with BCR::ABL1 levels < 0.01 % (MR4 IS) is allowed, however, it should not have been observed within the 9 months prior to randomization
Patient must meet the following laboratory values before randomization:
Absolute Neutrophil Count ≥ 1.5 x 10E9/L
Platelets ≥ 75 x 10E9/L
Hemoglobin ≥ 9 g/dL
Serum creatinine < 1.5 mg/dL
Total bilirubin ≤ 1.5 x ULN (Upper Limit of Normal) except for patients with Gilbert's syndrome who may only be included with total bilirubin ≤ 3.0 x ULN
Aspartate transaminase (AST) ≤ 3.0 x ULN
Alanine transaminase (ALT) ≤ 3.0 x ULN
Alkaline phosphatase ≤ 2.5 x ULN
Serum lipase ≤ 1.5 x ULN
Participants must have the following laboratory values ≥ Lower Limit of Normal or corrected to within normal limits with supplements prior to randomization: potassium increase of up to 6.0 mmol/L is acceptable if associated with creatinine clearance within normal limits ; calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable if associated with creatinine clearance* within normal limits) ; magnesium increase up to 3.0 mg/dL or 1.23 mmol/L if associated with creatinine clearance within normal limits.
Exclusion Criteria
Treatment failure according to European Leukemia Network (ELN) criteria 2013 during imatinib treatment.
Known second chronic phase of CML after previous progression to Accelerated Phase (AP)/Blast Crisis (BC).
Previous treatment with any tyrosine kinase inhibitors (TKIs) other than imatinib.
History or current diagnosis of ECG abnormalities indicating significant risk or safety for participants participating in the study such as:
History of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
Concomitant clinically significant arrhythmias
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
Concomitant medications with a "known" risk of Torsades de Pointes
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 medical history of chronic pancreatitis; on-going acute liver disease or history of 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.
Known second chronic phase of CML after previous progression to Accelerated Phase (AP)/Blast Crisis (BC).
Previous treatment with any tyrosine kinase inhibitors (TKIs) other than imatinib.
History or current diagnosis of ECG abnormalities indicating significant risk or safety for participants participating in the study such as:
History of myocardial infarction, angina pectoris, coronary artery bypass graft within 6 months prior to randomization
Concomitant clinically significant arrhythmias
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
Concomitant medications with a "known" risk of Torsades de Pointes
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 medical history of chronic pancreatitis; on-going acute liver disease or history of 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
