MedDataX Logo

Study of Efficacy and Safety of Asciminib in Combination With Imatinib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP)

NCT ID: NCT03578367

Last Updated: 2025-11-10

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-22

Study Completion Date

2025-02-26

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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)

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The study is a Phase 2, multi-center, open-label, randomized study of asciminib in two different doses (40 mg or 60 mg) in combination with imatinib 400 mg versus continued imatinib versus switch to nilotinib in Participants with chronic myeloid leukemia in chronic phase (CML-CP) who have been previously treated with imatinib first line therapy for at least one year and have not achieved deep molecular response (DMR). Eligible participants were randomized 1:1:1:1 to receive asciminib 60 mg once daily (QD) as add-on therapy to imatinib 400 mg QD, or 40 mg QD as add-on therapy to imatinib 400 mg QD, or to continue imatinib 400 mg QD, or to switch to nilotinib 300 mg twice a day (BID).

Participants on the imatinib continuation arm who had not achieved MR4.5 at 48 weeks were allowed to cross-over (CO) to receive the add-on treatment within 4 weeks after week 48 visit to receive the asciminib 60 mg combination add-on treatment, as this dose provided higher exposure. The cross-over is at the discretion of the investigator and the participant. Apart from a polymerase chain reaction (PCR) result of below MR4.5 at Week 48 visit, there are no other entry criteria for the cross-over part. Participants on nilotinib are not allowed to cross- over to receive the add-on treatment.

Participants on the study will continue on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) after the last participant received the first dose of treatment. After the last dose received, every participant will be followed up for safety for 30 days.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

CML Chronic Myelogenous Leukemia Leukemia, Myeloid Chronic Hematologic Diseases

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

CML Chronic Myelogenous Leukemia leukemia, myeloid chronic Hematologic Diseases Asciminib ABL001 Imatinib Nilotinib deep molecular response DMR Ph+ CML chronic phase cancer of the white blood cells tyrosine kinase inhibitor leukemia, myeloid leukemia CML with Ph+

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Treatment arms 1 - 4 randomized
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Asciminib 60mg QD + Imatinib 400mg QD

Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily

Group Type EXPERIMENTAL

Asciminib add-on

Intervention Type DRUG

Asciminib 60 mg or 40 mg taken orally once daily.

Imatinib

Intervention Type DRUG

Imatinib 400 mg taken orally once daily

Asciminib 40mg QD + Imatinib 400mg QD

Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily

Group Type EXPERIMENTAL

Asciminib add-on

Intervention Type DRUG

Asciminib 60 mg or 40 mg taken orally once daily.

Imatinib

Intervention Type DRUG

Imatinib 400 mg taken orally once daily

Imatinib 400mg QD

Imatinib 400 mg taken once daily

Group Type ACTIVE_COMPARATOR

Imatinib

Intervention Type DRUG

Imatinib 400 mg taken orally once daily

Nilotinib 300mg BID

Nilotinib 300 mg taken twice daily

Group Type ACTIVE_COMPARATOR

Nilotinib

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Asciminib add-on

Asciminib 60 mg or 40 mg taken orally once daily.

Intervention Type DRUG

Imatinib

Imatinib 400 mg taken orally once daily

Intervention Type DRUG

Nilotinib

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

ABL001 (asciminib) STI571 AMN107

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Georgia Regents University

Augusta, Georgia, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Novartis Investigative Site

Vienna, , Austria

Site Status

Novartis Investigative Site

Montreal, Quebec, Canada

Site Status

Novartis Investigative Site

Brno, , Czechia

Site Status

Novartis Investigative Site

Copenhagen, , Denmark

Site Status

Novartis Investigative Site

Bordeaux, , France

Site Status

Novartis Investigative Site

Dresden, , Germany

Site Status

Novartis Investigative Site

Milan, MI, Italy

Site Status

Novartis Investigative Site

Roma, RM, Italy

Site Status

Novartis Investigative Site

Krakow, , Poland

Site Status

Novartis Investigative Site

Warsaw, , Poland

Site Status

Novartis Investigative Site

Wroclaw, , Poland

Site Status

Novartis Investigative Site

Lisbon, , Portugal

Site Status

Novartis Investigative Site

Porto, , Portugal

Site Status

Novartis Investigative Site

Moscow, , Russia

Site Status

Novartis Investigative Site

Moscow, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Saint Petersburg, , Russia

Site Status

Novartis Investigative Site

Uijeongbu-si, Gyeonggi-do, South Korea

Site Status

Novartis Investigative Site

Seoul, Seocho Gu, South Korea

Site Status

Novartis Investigative Site

Seville, Andalusia, Spain

Site Status

Novartis Investigative Site

Badalona, Catalonia, Spain

Site Status

Novartis Investigative Site

Madrid, , Spain

Site Status

Novartis Investigative Site

Valencia, , Spain

Site Status

Novartis Investigative Site

Changhua, , Taiwan

Site Status

Novartis Investigative Site

Taoyuan District, , Taiwan

Site Status

Novartis Investigative Site

Liverpool, , United Kingdom

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Novartis Investigative Site

Oxford, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Australia Chile Hong Kong Japan United States Austria Canada Czechia Denmark France Germany Italy Poland Portugal Russia South Korea Spain Taiwan United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 39696526 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2018-001594-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-515040-23-00

Identifier Type: OTHER

Identifier Source: secondary_id

CABL001E2201

Identifier Type: -

Identifier Source: org_study_id