Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

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

ClinicalTrials.gov Identifier: NCT03578367

Novartis Reference Number: CABL001E2201

Last Update: Sep 21, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

To evaluate efficacy, safety and pharmacokinetic profile of asciminib 40mg+imatinib or asciminib 60mg+imatinib versus continued imatinib and versus nilotinib versus asciminib 80mg in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)

Condition 
CML
Chronic Myelogenous Leukemia
Leukemia, Myeloid Chronic
Hematologic Diseases
Phase 
Phase 2
Overall status 
Recruiting
Start date 
Nov 22, 2018
Completion date 
Dec 03, 2024
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
Asciminib add-on
Asciminib 60 mg or 40 mg taken orally once daily in addition to Imatinib 400 mg taken orally once daily
Drug
Imatinib
Imatinib 400 mg taken orally once daily
Drug
Nilotinib
Nilotinib 300 mg taken orally twice daily (total daily dose of 600 mg)
Drug
Asciminib single agent
Asciminib 80 mg taken orally once daily

Eligibility Criteria

Inclusion Criteria:

Male or female patients ≥ 18 years of age with a confirmed diagnosis of Chronic Myeloid Leukemia in chronic phase (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-ABL 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 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
Patients 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.

Key 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 kinese inhibitors (TKIs) other than imatinib.

History or current diagnosis of ECG abnormalities indicating significant risk or safety for subjects 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
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)
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
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.

Other protocol defined inclusion/exclusion may apply.

Study Locations

United States
Georgia Regents University
Recruiting
Augusta, 30912 - Georgia
Contact: Eleanor Katie Reeves (*see various departments*) - [email protected] -
United States
University of Chicago
Recruiting
Chicago, 60637 - Illinois
Contact: Belen M. Aguado (773-702-8582) - [email protected] - Richard A. Larson
United States
Austria
Novartis Investigative Site
Recruiting
Wien, 1140
-
Austria
Canada
Novartis Investigative Site
Recruiting
Montreal, H1T 2M4
Quebec
Canada
Czech Republic
Novartis Investigative Site
Recruiting
Brno - Bohunice, 625 00
-
Czech Republic
Korea, Republic of
Novartis Investigative Site
Recruiting
Uijeongbu si, 11759
Gyeonggi Do
Korea, Republic of
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41009
Andalucia
Spain
Novartis Investigative Site
Recruiting
Madrid, 28034
-
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
-
Spain
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
United Kingdom
Novartis Investigative Site
Recruiting
Wirral, CH63 4JY
Merseyside
United Kingdom
Novartis Investigative Site
Recruiting
London, W12 0HS
-
United Kingdom

Contacts

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Phone: 
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