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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03578367
Ethics application status
Date submitted
15/06/2018
Date registered
6/07/2018

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

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.

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 at 48 Weeks
Timepoint [1] 0 0
at Week 48
Secondary outcome [1] 0 0
Rate of MR^4.5 at 48 Weeks
Timepoint [1] 0 0
at Week 48
Secondary outcome [2] 0 0
Rate of MR^4.5 by 48 Weeks
Timepoint [2] 0 0
by 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 96 Weeks
Timepoint [4] 0 0
by 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
96/48 weeks after the last rand./enrolled (asciminib 80mg cohort) participant received the first study dose
Secondary outcome [7] 0 0
Duration of MR^4.5
Timepoint [7] 0 0
96/48 weeks after the last rand./enrolled (asciminib 80mg cohort) participant received the first study dose
Secondary outcome [8] 0 0
Pharmacokinetic Profile of Asciminib and Imatinib When Administered in Combination - Cmax
Timepoint [8] 0 0
up to 96 weeks
Secondary outcome [9] 0 0
Pharmacokinetic Profile of Asciminib and Imatinib When Administered in Combination - Tmax
Timepoint [9] 0 0
up to 96 weeks
Secondary outcome [10] 0 0
Pharmacokinetic Profile of Asciminib and Imatinib When Administered in Combination - Cmin
Timepoint [10] 0 0
up to 96 weeks
Secondary outcome [11] 0 0
Pharmacokinetic Profile of Asciminib and Imatinib When Administered in Combination - AUClast
Timepoint [11] 0 0
up to 96 weeks
Secondary outcome [12] 0 0
Pharmacokinetic Profile of Asciminib and Imatinib When Administered in Combination - AUCtau
Timepoint [12] 0 0
up to 96 weeks
Secondary outcome [13] 0 0
MR^4.5 Rate at 48 Weeks
Timepoint [13] 0 0
at 48 weeks
Secondary outcome [14] 0 0
Pharmacokinetic Profile of Asciminib 80mg QD - Cmax
Timepoint [14] 0 0
up to 48 weeks
Secondary outcome [15] 0 0
Pharmacokinetic Profile of Asciminib 80mg QD - Tmax
Timepoint [15] 0 0
up to 48 weeks
Secondary outcome [16] 0 0
Pharmacokinetic Profile of Asciminib 80mg QD - Cmin
Timepoint [16] 0 0
up to 48 weeks
Secondary outcome [17] 0 0
Pharmacokinetic Profile of Asciminib 80mg QD - AUClast
Timepoint [17] 0 0
up to 48 weeks
Secondary outcome [18] 0 0
Pharmacokinetic Profile of Asciminib 80mg QD - AUCtau
Timepoint [18] 0 0
up to 48 weeks

Eligibility
Key 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 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.

* 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
* Participantss 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
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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 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.

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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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
Actual
26/02/2025
Sample size
Target
Accrual to date
Final
104
Recruitment in Australia
Recruitment state(s)
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
Maryland
Country [3] 0 0
Austria
State/province [3] 0 0
Wien
Country [4] 0 0
Canada
State/province [4] 0 0
Quebec
Country [5] 0 0
Czechia
State/province [5] 0 0
Brno Bohunice
Country [6] 0 0
Denmark
State/province [6] 0 0
Copenhagen
Country [7] 0 0
France
State/province [7] 0 0
Bordeaux
Country [8] 0 0
Germany
State/province [8] 0 0
Dresden
Country [9] 0 0
Italy
State/province [9] 0 0
MI
Country [10] 0 0
Italy
State/province [10] 0 0
RM
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Gyeonggi Do
Country [12] 0 0
Korea, Republic of
State/province [12] 0 0
Seocho Gu
Country [13] 0 0
Poland
State/province [13] 0 0
Krakow
Country [14] 0 0
Poland
State/province [14] 0 0
Warszawa
Country [15] 0 0
Poland
State/province [15] 0 0
Wroclaw
Country [16] 0 0
Portugal
State/province [16] 0 0
Lisboa
Country [17] 0 0
Portugal
State/province [17] 0 0
Porto
Country [18] 0 0
Russian Federation
State/province [18] 0 0
Moscow
Country [19] 0 0
Russian Federation
State/province [19] 0 0
Saint Petersburg
Country [20] 0 0
Spain
State/province [20] 0 0
Andalucia
Country [21] 0 0
Spain
State/province [21] 0 0
Catalunya
Country [22] 0 0
Spain
State/province [22] 0 0
Madrid
Country [23] 0 0
Spain
State/province [23] 0 0
Valencia
Country [24] 0 0
Taiwan
State/province [24] 0 0
Changhua
Country [25] 0 0
Taiwan
State/province [25] 0 0
Taoyuan
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Liverpool
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Oxford

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT03578367