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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03578367




Registration number
NCT03578367
Ethics application status
Date submitted
15/06/2018
Date registered
3/07/2018
Date last updated
6/02/2019

Titles & IDs
Public title
Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)
Scientific title
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
Secondary ID [1] 0 0
CABL001E2201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
CML 0 0
Chronic Myelogenous Leukemia 0 0
Leukemia, Myeloid Chronic 0 0
Hematologic Diseases 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Asciminib add-on
Treatment: Drugs - Imatinib
Treatment: Drugs - Nilotinib

Experimental: Asciminib 60mg QD + Imatinib 400mg QD - Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily

Experimental: Asciminib 40mg QD + Imatinib 400mg QD - Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily

Active Comparator: Imatinib 400mg QD - Imatinib 400 mg taken once daily

Active Comparator: Nilotinib 300mg BID - Nilotinib 300 mg taken twice daily


Treatment: Drugs: Asciminib add-on
Asciminib 60 mg or 40 mg taken orally once daily in addition to Imatinib 400 mg taken orally once daily

Treatment: Drugs: Imatinib
Imatinib 400 mg taken orally once daily

Treatment: Drugs: Nilotinib
Nilotinib 300 mg taken orally twice daily (total daily dose of 600 mg)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Molecular Response (MR)^4.5 rate between asciminib+imatinib and imatinib alone - Difference in the proportion of subjects with MR^4.5 (BCR-ABL1 (Fusion gene from breakpoint cluster region and Abelson genes) ratio of = 0.0032%) at 48 weeks between asciminib+imatinib and imatinib alone
Timepoint [1] 0 0
at 48 weeks
Secondary outcome [1] 0 0
MR^4.5 rate 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
Timepoint [1] 0 0
at 48 weeks
Secondary outcome [2] 0 0
Rate of MR^4.5 at 96 weeks - Proportion of subjects with MR^4.5 (BCR-ABL1 ratio of = 0.0032%) at 96 weeks
Timepoint [2] 0 0
at 96 weeks
Secondary outcome [3] 0 0
Rate of MR^4.5 by 48 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
Timepoint [3] 0 0
by 48 weeks and 96 weeks
Secondary outcome [4] 0 0
Sustained MR^4.5 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.
Timepoint [4] 0 0
from 48 weeks until 96 weeks
Secondary outcome [5] 0 0
Time to MR^4.5 - 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
Timepoint [5] 0 0
up to 96 weeks
Secondary outcome [6] 0 0
Difference in rate of MR^4.5 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
Timepoint [6] 0 0
at 48 weeks
Secondary outcome [7] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax - The maximum (peak) observed drug concentration after dose administration
Timepoint [7] 0 0
up to Week 4 Day 28
Secondary outcome [8] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax - The time to reach maximum (peak) drug concentration after dose administration
Timepoint [8] 0 0
up to Week 4 Day 28
Secondary outcome [9] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin - Minimum drug concentration
Timepoint [9] 0 0
up to 96 weeks
Secondary outcome [10] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast - The AUC from time zero to the last measurable concentration sampling time (Tlast)
Timepoint [10] 0 0
up to Week 4 Day 28
Secondary outcome [11] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau - The AUC calculated to the end of a dosing interval (tau) at steady-state
Timepoint [11] 0 0
up to Week 4 Day 28

Eligibility
Key inclusion criteria
1. Male or female patients = 18 years of age with a confirmed diagnosis of Chronic
Myeloid Leukemia in chronic phase (CML-CP).

2. Minimum of two years (24 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).

3. BCR-ABL1 levels > 0.01% IS (International Scale) 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.

4. 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

5. Patients must have the following laboratory values = Lower Limit of Normal or
corrected to within normal limits with supplements prior to randomization: potassium,
magnesium, phosphorus, total calcium (corrected for serum albumin).

Key
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Treatment failure according to European Leukemia Network (ELN) criteria 2013 during
imatinib treatment.

2. Known second chronic phase of CML after previous progression to Accelerated Phase
(AP)/Blast Crisis (BC).

3. Previous treatment with any tyrosine kinese inhibitors (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, 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 past medical
history of chronic pancreatitis.

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.

Other protocol defined inclusion/exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Adelaide
Recruitment postcode(s) [1] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Maryland
Country [2] 0 0
Czechia
State/province [2] 0 0
Brno - Bohunice
Country [3] 0 0
France
State/province [3] 0 0
Bordeaux
Country [4] 0 0
Hong Kong
State/province [4] 0 0
Hong Kong
Country [5] 0 0
Japan
State/province [5] 0 0
Tokyo
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seocho-gu
Country [7] 0 0
Spain
State/province [7] 0 0
Andalucia
Country [8] 0 0
Spain
State/province [8] 0 0
Las Palmas de Gran Canaria
Country [9] 0 0
Spain
State/province [9] 0 0
Valencia
Country [10] 0 0
Taiwan
State/province [10] 0 0
Changhua
Country [11] 0 0
Taiwan
State/province [11] 0 0
Taipei
Country [12] 0 0
United Kingdom
State/province [12] 0 0
London
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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)
Trial website
https://clinicaltrials.gov/show/NCT03578367
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
novartis.email@novartis.com
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable