Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Who Have Been Previously Treated With Imatinib and Have Not Achieved Deep Molecular Response.
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
3 other identifiers
interventional
104
15 countries
30
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). An asciminib single agent arm (80 mg daily) was added after the primary analysis to evaluate if asciminib alone could lead to MR4.5 patients in Imatinib for at least one year who have never achieved deep molecular response (DMR).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2018
Longer than P75 for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 15, 2018
CompletedFirst Posted
Study publicly available on registry
July 6, 2018
CompletedStudy Start
First participant enrolled
November 22, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 8, 2021
CompletedResults Posted
Study results publicly available
February 14, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
February 26, 2025
CompletedApril 21, 2026
April 1, 2026
3 years
June 15, 2018
October 4, 2024
April 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Molecular Response (MR)^4.5 Rate at 48 Weeks and Difference in Rate Between Asciminib + Imatinib and Imatinib Alone
Percentage of participants still treated with the randomized treatment at 48 weeks and are in MR\^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks (± assessment window), among all participants in the asciminib add-on arms vs imatinib arm.
at Week 48
Secondary Outcomes (20)
Rate of MR^4.5 at 48 Weeks (Asciminib add-on Arms vs Nilotinib)
at Week 48
Rate of MR^4.5 by 48 Weeks (Randomized Arms)
by 48 weeks
Rate of MR^4.5 at 96 Weeks (Randomized Arms) and Difference in Rate Between Asciminib + Imatinib and Nilotinib Alone
at Week 96
Rate of MR^4.5 by 96 Weeks (Randomized Arms)
by 96 weeks
Sustained MR^4.5 From at 96 Weeks (Randomized Arms)
at 96 weeks
- +15 more secondary outcomes
Study Arms (5)
Asciminib 60mg QD + Imatinib 400mg QD
EXPERIMENTALAsciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily
Asciminib 40mg QD + Imatinib 400mg QD
EXPERIMENTALAsciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily
Imatinib 400mg QD
ACTIVE COMPARATORImatinib 400 mg taken once daily
Nilotinib 300mg BID
ACTIVE COMPARATORNilotinib 300 mg taken twice daily
Asciminib 80mg QD (ASAC)
EXPERIMENTALAsciminib 80 mg taken once daily
Interventions
Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily.
Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily.
Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules and taken orally twice daily.
Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily (in the fasted state) on a continuous schedule (QD).
Eligibility Criteria
You may qualify if:
- Male or female patients ≥ 18 years of age with a confirmed diagnosis of 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::ABL1 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 1 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
- +2 more criteria
You may not qualify if:
- 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 kinase 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
Georgia Regents University
Augusta, Georgia, 30912, United States
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21205, United States
Novartis Investigative Site
Vienna, 1140, Austria
Novartis Investigative Site
Montreal, Quebec, H1T 2M4, Canada
Novartis Investigative Site
Brno, 625 00, Czechia
Novartis Investigative Site
Copenhagen, DK-2100, Denmark
Novartis Investigative Site
Bordeaux, 33076, France
Novartis Investigative Site
Dresden, 01307, Germany
Novartis Investigative Site
Milan, MI, 20162, Italy
Novartis Investigative Site
Roma, RM, 00161, Italy
Novartis Investigative Site
Krakow, 31 531, Poland
Novartis Investigative Site
Warsaw, 00-791, Poland
Novartis Investigative Site
Wroclaw, 50 367, Poland
Novartis Investigative Site
Lisbon, 1099-023, Portugal
Novartis Investigative Site
Porto, 4200-072, Portugal
Novartis Investigative Site
Moscow, 125167, Russia
Novartis Investigative Site
Moscow, 125284, Russia
Novartis Investigative Site
Saint Petersburg, 191024, Russia
Novartis Investigative Site
Saint Petersburg, 197341, Russia
Novartis Investigative Site
Uijeongbu-si, Gyeonggi-do, 11759, South Korea
Novartis Investigative Site
Seoul, 06591, South Korea
Novartis Investigative Site
Badalona, Barcelona, 08916, Spain
Novartis Investigative Site
Madrid, 28034, Spain
Novartis Investigative Site
Seville, 41009, Spain
Novartis Investigative Site
Valencia, 46026, Spain
Novartis Investigative Site
Changhua, 50006, Taiwan
Novartis Investigative Site
Taoyuan District, 33305, Taiwan
Novartis Investigative Site
Liverpool, CH63 4JY, United Kingdom
Novartis Investigative Site
London, W12 0HS, United Kingdom
Novartis Investigative Site
Oxford, OX3 7LE, United Kingdom
Related Publications (1)
Hughes TP, Saglio G, Geissler J, Kim DW, Lomaia E, Mayer J, Turkina A, Kapoor S, Cardoso AP, Nieman B, Quenet S, Cortes JE. Asciminib add-on to imatinib demonstrates sustained high rates of ongoing therapy and deep molecular responses with prolonged follow-up in the ASC4MORE study. J Hematol Oncol. 2024 Dec 18;17(1):125. doi: 10.1186/s13045-024-01642-6.
PMID: 39696526DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The use of zero (0) in the post-treatment period indicates adverse events were not collected.
Results Point of Contact
- Title
- Clinical Disclosure Office
- Organization
- Novartis Pharmaceuticals
Study Officials
- STUDY DIRECTOR
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 15, 2018
First Posted
July 6, 2018
Study Start
November 22, 2018
Primary Completion
November 8, 2021
Study Completion
February 26, 2025
Last Updated
April 21, 2026
Results First Posted
February 14, 2025
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.