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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03578367




Registration number
NCT03578367
Ethics application status
Date submitted
15/06/2018
Date registered
6/07/2018
Date last updated
3/01/2024

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
2018-001594-24
Secondary ID [2] 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
Treatment: Drugs - Asciminib single agent

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

Experimental: Asciminib 80mg QD - Asciminib 80 mg taken once daily


Treatment: Drugs: Asciminib add-on
Asciminib 60 mg or 40 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)

Treatment: Drugs: Asciminib single agent
Asciminib 80 mg taken orally once daily
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
Timepoint [1] 0 0
at 48 weeks
Secondary outcome [1] 0 0
MR^4.5 rate at 48 weeks
Timepoint [1] 0 0
at 48 weeks
Secondary outcome [2] 0 0
Difference in rate of MR^4.5 at 48 weeks
Timepoint [2] 0 0
at 48 weeks
Secondary outcome [3] 0 0
Rate of MR^4.5 at 96 weeks
Timepoint [3] 0 0
at 96 weeks
Secondary outcome [4] 0 0
Rate of MR^4.5 by 48 and 96 weeks
Timepoint [4] 0 0
by 48 weeks and 96 weeks
Secondary outcome [5] 0 0
Sustained MR^4.5 from 48 weeks until 96 weeks
Timepoint [5] 0 0
at 96 weeks
Secondary outcome [6] 0 0
Time to MR^4.5
Timepoint [6] 0 0
up to 96 weeks
Secondary outcome [7] 0 0
Duration of MR^4.5
Timepoint [7] 0 0
end of treatment
Secondary outcome [8] 0 0
Incidence and severity of adverse events, changes in laboratory values, clinically notable ECG abnormalities and vital signs
Timepoint [8] 0 0
end of study
Secondary outcome [9] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmax
Timepoint [9] 0 0
up to 96 weeks
Secondary outcome [10] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Tmax
Timepoint [10] 0 0
up to 96 weeks
Secondary outcome [11] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - Cmin
Timepoint [11] 0 0
up to 96 weeks
Secondary outcome [12] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUClast
Timepoint [12] 0 0
up to 96 weeks
Secondary outcome [13] 0 0
Pharmacokinetic profile of asciminib and imatinib when administered in combination - AUCtau
Timepoint [13] 0 0
up to 96 weeks
Secondary outcome [14] 0 0
MR^4.5 rate at 48 weeks
Timepoint [14] 0 0
at 48 weeks
Secondary outcome [15] 0 0
Time to MR^4.5
Timepoint [15] 0 0
up to 48 weeks
Secondary outcome [16] 0 0
Duration of MR^4.5
Timepoint [16] 0 0
end of treatment
Secondary outcome [17] 0 0
Pharmacokinetic profile of asciminib 80mg QD - Cmax
Timepoint [17] 0 0
up to 48 weeks
Secondary outcome [18] 0 0
Pharmacokinetic profile of asciminib 80mg QD - Tmax
Timepoint [18] 0 0
up to 48 weeks
Secondary outcome [19] 0 0
Pharmacokinetic profile of asciminib 80mg QD - Cmin
Timepoint [19] 0 0
up to 48 weeks
Secondary outcome [20] 0 0
Pharmacokinetic profile of asciminib 80mg QD - AUClast
Timepoint [20] 0 0
up to 48 weeks
Secondary outcome [21] 0 0
Pharmacokinetic profile of asciminib 80mg QD - AUCtau
Timepoint [21] 0 0
up to 48 weeks

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 one year (12 calendar months) treatment with imatinib first line for CML-CP
(patients have to be on imatinib 300mg or 400 mg QD at randomization

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.

3. 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

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

- Serum lipase = 1.5 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
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
Minimum age
18 Years
Maximum age
No limit
Sex
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 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.

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
22/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
4/04/2025
Actual
Sample size
Target
104
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Adelaide
Recruitment hospital [3] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Austria
State/province [6] 0 0
Graz
Country [7] 0 0
Austria
State/province [7] 0 0
Wien
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Chile
State/province [9] 0 0
Araucania
Country [10] 0 0
Chile
State/province [10] 0 0
Valparaiso
Country [11] 0 0
Czechia
State/province [11] 0 0
Brno - Bohunice
Country [12] 0 0
Denmark
State/province [12] 0 0
Copenhagen
Country [13] 0 0
France
State/province [13] 0 0
Bordeaux
Country [14] 0 0
Germany
State/province [14] 0 0
Baden Wuerttemberg
Country [15] 0 0
Germany
State/province [15] 0 0
Berlin
Country [16] 0 0
Germany
State/province [16] 0 0
Dresden
Country [17] 0 0
Hong Kong
State/province [17] 0 0
Hong Kong
Country [18] 0 0
Italy
State/province [18] 0 0
BO
Country [19] 0 0
Italy
State/province [19] 0 0
MI
Country [20] 0 0
Italy
State/province [20] 0 0
RM
Country [21] 0 0
Japan
State/province [21] 0 0
Tokyo
Country [22] 0 0
Korea, Republic of
State/province [22] 0 0
Gyeonggi Do
Country [23] 0 0
Korea, Republic of
State/province [23] 0 0
Seocho Gu
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Poland
State/province [25] 0 0
Krakow
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
Poland
State/province [27] 0 0
Wroclaw
Country [28] 0 0
Portugal
State/province [28] 0 0
Lisboa
Country [29] 0 0
Portugal
State/province [29] 0 0
Porto
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Moscow
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Saint Petersburg
Country [32] 0 0
Spain
State/province [32] 0 0
Andalucia
Country [33] 0 0
Spain
State/province [33] 0 0
Catalunya
Country [34] 0 0
Spain
State/province [34] 0 0
Las Palmas de Gran Canaria
Country [35] 0 0
Spain
State/province [35] 0 0
Madrid
Country [36] 0 0
Spain
State/province [36] 0 0
Valencia
Country [37] 0 0
Taiwan
State/province [37] 0 0
Changhua
Country [38] 0 0
Taiwan
State/province [38] 0 0
Taipei
Country [39] 0 0
Taiwan
State/province [39] 0 0
Taoyuan
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Merseyside
Country [41] 0 0
United Kingdom
State/province [41] 0 0
London
Country [42] 0 0
United Kingdom
State/province [42] 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 versus asciminib 80mg
in pre-treated patients with Chronic Myeloid Leukemia in chronic phase (CML-CP)
Trial website
https://clinicaltrials.gov/ct2/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
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03578367