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

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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 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
Enrollment count 
80 participants
Start date 
Nov 22, 2018
Completion date 
Nov 23, 2022
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)

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
United States
University of Chicago
Recruiting
Chicago, 60637
Illinois
United States
Sidney Kimmel Comprehensive Cancer Center
Recruiting
Baltimore, 21205
Maryland
United States
Saint Agnes Healthcare Cancer Institute
Recruiting
Baltimore, 21229
Maryland
United States
SUNY Stony Brook Medical Oncology Hematology/Oncology
Recruiting
Stony Brook, 11794-8174
New York
United States
University of Texas MD Anderson Cancer Center
Recruiting
Houston, 77030
Texas
United States
Australia
Novartis Investigative Site
Recruiting
Darlinghurst, 2010
New South Wales
Australia
Novartis Investigative Site
Recruiting
Adelaide, 5000
South Australia
Australia
Novartis Investigative Site
Recruiting
Melbourne, 3000
Victoria
Australia
Austria
Novartis Investigative Site
Recruiting
Graz, 8036
-
Austria
Novartis Investigative Site
Recruiting
Wien, 1140
-
Austria
Canada
Novartis Investigative Site
Recruiting
Montreal, H1T 2M4
Quebec
Canada
Chile
Novartis Investigative Site
Active, not recruiting
Temuco, 4810469
Araucania
Chile
Novartis Investigative Site
Recruiting
Vina del Mar, 2540364
Valparaiso
Chile
Czechia
Novartis Investigative Site
Recruiting
Brno - Bohunice, 639 01
-
Czechia
Denmark
Novartis Investigative Site
Recruiting
Herlev, DK 2730
-
Denmark
France
Novartis Investigative Site
Recruiting
Bordeaux, 33076
-
France
Germany
Novartis Investigative Site
Recruiting
Mannheim, 68305
Baden-Wuerttemberg
Germany
Novartis Investigative Site
Recruiting
Berlin, 13353
-
Germany
Novartis Investigative Site
Recruiting
Dresden, 01307
-
Germany
Hong Kong
Novartis Investigative Site
Recruiting
Hong Kong,
-
Hong Kong
Italy
Novartis Investigative Site
Withdrawn
Bologna, 40138
BO
Italy
Novartis Investigative Site
Active, not recruiting
Milano, 20162
MI
Italy
Novartis Investigative Site
Recruiting
Roma, 00161
RM
Italy
Japan
Novartis Investigative Site
Withdrawn
Shinagawa ku, 141 8625
Tokyo
Japan
Korea, Republic of
Novartis Investigative Site
Active, not recruiting
Seoul, 06591
Seocho Gu
Korea, Republic of
Novartis Investigative Site
Recruiting
Seoul, 03080
-
Korea, Republic of
Poland
Novartis Investigative Site
Recruiting
Krakow, 31 531
-
Poland
Novartis Investigative Site
Active, not recruiting
Warszawa, 02 776
-
Poland
Novartis Investigative Site
Recruiting
Wroclaw, 50 367
-
Poland
Portugal
Novartis Investigative Site
Recruiting
Lisboa, 1099 023
-
Portugal
Novartis Investigative Site
Recruiting
Porto, 4200-072
-
Portugal
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 125167
-
Russian Federation
Novartis Investigative Site
Recruiting
Moscow, 125284
-
Russian Federation
Novartis Investigative Site
Recruiting
Saint Petersburg, 191024
-
Russian Federation
Novartis Investigative Site
Recruiting
Saint Petersburg, 197341
-
Russian Federation
Spain
Novartis Investigative Site
Recruiting
Sevilla, 41009
Andalucia
Spain
Novartis Investigative Site
Withdrawn
Las Palmas de Gran Canaria, 35010
-
Spain
Novartis Investigative Site
Recruiting
Madrid, 28034
-
Spain
Novartis Investigative Site
Recruiting
Valencia, 46026
-
Spain
Taiwan
Novartis Investigative Site
Recruiting
Changhua, 50006
-
Taiwan
Novartis Investigative Site
Recruiting
Taipei, 10002
-
Taiwan
Novartis Investigative Site
Recruiting
Taoyuan, 33305
-
Taiwan
United Kingdom
Novartis Investigative Site
Recruiting
Wirral, CH63 4JY
Merseyside
United Kingdom
Novartis Investigative Site
Recruiting
London, W12 0HS
-
United Kingdom
Novartis Investigative Site
Recruiting
Oxford, OX3 7LJ
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
1-888-669-6682
Name: 
Novartis Pharmaceuticals
Phone: 
+41613241111
Email: 

Have a question?

Call 1-999-669-6682 or email [email protected]