CMLPhase 2NCT03578367
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 study testing Asciminib add-on, Imatinib and Nilotinib in people with CML and Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 30 sites in 15 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- CML, Chronic Myelogenous Leukemia, Leukemia, Myeloid Chronic
- What is being tested?
- Asciminib add-on, Imatinib and Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 30 sitesin 15 countries
- Study dates
- 22 Nov 2018to 26 Feb 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
- 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
Show all 17Show fewer
- 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
- Participants 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.
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
30 sites in 15 countries.
30 sites in 15 countries
Russia4 sites
Novartis Investigative Site
Moscow, 125167
Novartis Investigative Site
Moscow, 125284
Novartis Investigative Site
Saint Petersburg, 191024
Novartis Investigative Site
Saint Petersburg, 197341
Spain4 sites
Novartis Investigative Site
Badalona, Barcelona, 08916
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Seville, 41009
Novartis Investigative Site
Valencia, 46026
Poland3 sites
Novartis Investigative Site
Krakow, 31 531
Novartis Investigative Site
Warsaw, 00-791
Novartis Investigative Site
Wroclaw, 50 367
United Kingdom3 sites
Novartis Investigative Site
Liverpool, CH63 4JY
Novartis Investigative Site
London, W12 0HS
Novartis Investigative Site
Oxford, OX3 7LE
United States2 sites
Georgia Regents University
Augusta, Georgia, 30912
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21205
Italy2 sites
Novartis Investigative Site
Milan, MI, 20162
Novartis Investigative Site
Roma, RM, 00161
Portugal2 sites
Novartis Investigative Site
Lisbon, 1099-023
Novartis Investigative Site
Porto, 4200-072
South Korea2 sites
Novartis Investigative Site
Seoul, 06591
Novartis Investigative Site
Uijeongbu-si, Gyeonggi-do, 11759
Taiwan2 sites
Novartis Investigative Site
Changhua, 50006
Novartis Investigative Site
Taoyuan, 33305
About this study
Official 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
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).
Read the detailed description
The study was 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 had been previously treated with imatinib first line therapy for at least one year and had 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). During the trial, there was no switch allowed. It was just at the moment of the randomization that the participants were selected to asciminib add-on arms or nilotinib.
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 was 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 were no other entry criteria for the cross-over part. Participants on nilotinib were not allowed to cross-over to receive the add-on treatment.
Participants on the study continued on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) after the last participant had received the first dose of treatment. After the last dose was received, every participant was followed up for safety for 30 days.
- Being tested
- Asciminib add-on, Imatinib, Nilotinib, Asciminib 80mg QD (asciminib single agent (ASAC))
- Keywords
- 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+
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Hematologic Diseases, Leukemia, Myeloid, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Asciminib add-onDrug
Also called ABL001 (asciminib)
Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily.
ImatinibDrug
Also called STI571
Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily.
NilotinibDrug
Also called AMN107
Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules and taken orally twice daily.
Asciminib 80mg QD (asciminib single agent (ASAC))Drug
Also called ABL001
Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily (in the fasted state) on a continuous schedule (QD).
| Study group | Role | What they receive |
|---|---|---|
| Asciminib 60mg QD + Imatinib 400mg QD | Experimental | Asciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily Receives: Drug: Asciminib add-on; Drug: Imatinib |
| Asciminib 40mg QD + Imatinib 400mg QD | Experimental | Asciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily Receives: Drug: Asciminib add-on; Drug: Imatinib |
| Imatinib 400mg QD | Active comparator | Imatinib 400 mg taken once daily Receives: Drug: Imatinib |
| Nilotinib 300mg BID | Active comparator | Nilotinib 300 mg taken twice daily Receives: Drug: Nilotinib |
| Asciminib 80mg QD (ASAC) | Experimental | Asciminib 80 mg taken once daily Receives: Drug: Asciminib 80mg QD (asciminib single agent (ASAC)) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at Week 48
Secondary outcomes (20)
Rate of MR^4.5 at 48 Weeks (Asciminib add-on Arms vs Nilotinib)
Percentage of participants in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks in asciminib add-on arms vs nilotinib arm.
Measured: at Week 48
Rate of MR^4.5 by 48 Weeks (Randomized Arms)
Best observed MR^4.5 rate (BCR::ABL1 ratio of ≤ 0.0032%) up to 48 weeks, i.e. the percentage of participants who achieved MR 4.5 anytime up to 48 weeks.
Measured: by 48 weeks
Rate of MR^4.5 at 96 Weeks (Randomized Arms) and Difference in Rate Between Asciminib + Imatinib and Nilotinib Alone
Percentage of participants in MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 96 weeks in asciminib add-on arms vs nilotinib arm.
Measured: at Week 96
Rate of MR^4.5 by 96 Weeks (Randomized Arms)
Best observed MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) rate up to 96 weeks, i.e. the percentage of participants who achieved MR^4.5 anytime up to 96 weeks.
Measured: by 96 weeks
Sustained MR^4.5 From at 96 Weeks (Randomized Arms)
Sustained MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) rate was defined as the percentage of participants who were in MR4.5 at 48 weeks and 96 weeks and who had no loss of MR4.5 in between those 2 time points.
Measured: at 96 weeks
Time to MR^4.5 (Randomized Arms)
Time to MR^4.5 is the time from first dose to first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) computed only for participants who achieved MR^4.5 at least once before the cut-off date.
Measured: 96 weeks after the last participant received the first study dose
Duration of MR^4.5 (Randomized Arms)
Duration of MR^4.5 was defined as the time from the first documented MR^4.5 and the end date of MR^4.5, i.e., the earliest date of loss of MR^4.5 or CML-related death. Confirmed loss of MR^4.5 is defined as an increase of the BCR::ABL1 ratio to >0.0032% in two consecutive blood samples, by International Scale.
Measured: 96 weeks after the last participant received the first study dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmax (Randomized Arms)
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (mass x volume-1).
Measured: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Tmax (Randomized Arms)
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug concentration after single dose administration (time).
Measured: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmin (Randomized Arms)
Minimum drug plasma(serum/blood) concentration
Measured: Week 2 Day 14: pre-dose (0h), Week 4 Day 28: pre-dose (0h)
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUClast (Randomized Arms)
The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1).
Measured: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUCtau (Randomized Arms)
The AUC calculated to the end of a dosing interval (tau) at steady-state
Measured: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Molecular Response (MR) 4.5 Rate at 48 Weeks (Asciminib Single Agent Cohort (ASAC))
Percentage of participants on asciminib 80 mg QD with MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) at 48 weeks.
Measured: at Week 48
Time to MR^4.5 (ASAC)
Time from first dose of asciminib 80 mg QD to first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) computed only for participants who achieved MR^4.5.
Measured: 48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Duration of MR^4.5 (ASAC)
Time from first MR^4.5 (BCR::ABL1 ratio of ≤ 0.0032%) until confirmed loss of MR^4.5 or CML-related death.
Measured: 48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmax (ASAC)
The maximum (peak) observed plasma drug concentration after oral dose administration (mass x volume-1).
Measured: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Tmax (ASAC)
The time to reach maximum (Cmax) plasma drug concentration after oral dose administration (time).
Measured: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmin (ASAC)
Minimum drug plasma (serum/blood) concentration
Measured: Week 2 Day 14: 0h (pre-dose), Week 4 Day 28: 0h (pre-dose)
Pharmacokinetic Profile of Asciminib 80mg QD - AUClast (ASAC)
The AUC from time zero to the last measurable concentration sampling time (Tlast) (mass x time x volume-1).
Measured: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - AUCtau (ASAC)
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x time x volume-1)
Measured: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2018
- Study start22 Nov 2018
- Primary completion8 Nov 2021
- Study completion26 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CMLStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Treatment arms 1 - 4 randomized (84 participants) and asciminib single agent cohort, not randomized (20 participants)
- Masking
- None (open label)
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03578367
- Sponsor's protocol ID
- CABL001E2201
- Other IDs
- 2018-001594-24, 2024-515040-23-00, 2018
- Status last verified
- Apr 2026
- First submitted
- 15 Jun 2018
- Last updated
- 21 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39696526
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03578367
- Acronym / sponsor ID
- CABL001E2201
- Keywords
- CML, Chronic Myelogenous Leukemia, leukemia, myeloid chronic, Hematologic Diseases, Asciminib, ABL001, Imatinib, Nilotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 22 Nov 2018 (actual)
- Primary completion
- 8 Nov 2021 (actual)
- Study completion
- 26 Feb 2025 (actual)
- First posted
- 6 Jul 2018 (actual)
- Results
- Posted 14 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The study was 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 had been previously treated with imatinib first line therapy for at least one year and had 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). During the trial, there was no switch allowed. It was just at the moment of the randomization that the participants were selected to asciminib add-on arms or nilotinib.
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 was 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 were no other entry criteria for the cross-over part. Participants on nilotinib were not allowed to cross-over to receive the add-on treatment.
Participants on the study continued on the allocated treatment until treatment failure, intolerability, or for up to 96 weeks (in arms 1 to 4) after the last participant had received the first dose of treatment. After the last dose was received, every participant was followed up for safety for 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- Treatment arms 1 - 4 randomized (84 participants) and asciminib single agent cohort, not randomized (20 participants)
| Arm | Type | Receives |
|---|---|---|
| Asciminib 60mg QD + Imatinib 400mg QD | Experimental | Drug: Asciminib add-on, Drug: ImatinibAsciminib 60 mg taken once daily in combination with Imatinib 400 mg taken once daily |
| Asciminib 40mg QD + Imatinib 400mg QD | Experimental | Drug: Asciminib add-on, Drug: ImatinibAsciminib 40 mg taken once daily in combination with Imatinib 400 mg taken once daily |
| Imatinib 400mg QD | Active comparator | Drug: ImatinibImatinib 400 mg taken once daily |
| Nilotinib 300mg BID | Active comparator | Drug: NilotinibNilotinib 300 mg taken twice daily |
| Asciminib 80mg QD (ASAC) | Experimental | Drug: Asciminib 80mg QD (asciminib single agent (ASAC))Asciminib 80 mg taken once daily |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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).
- 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.
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Asciminib add-onAlso: ABL001 (asciminib)Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily. | Drug | Asciminib 40mg QD + Imatinib 400mg QD, Asciminib 60mg QD + Imatinib 400mg QD |
| ImatinibAlso: STI571Imatinib was supplied as 400 mg and 100 mg tablets and taken orally once daily. | Drug | Asciminib 40mg QD + Imatinib 400mg QD, Asciminib 60mg QD + Imatinib 400mg QD, Imatinib 400mg QD |
| NilotinibAlso: AMN107Nilotinib was supplied as 150 mg and 200 mg hard gelatin capsules and taken orally twice daily. | Drug | Nilotinib 300mg BID |
| Asciminib 80mg QD (asciminib single agent (ASAC))Also: ABL001Asciminib was supplied as 40 mg and 20 mg tablets and taken orally once daily (in the fasted state) on a continuous schedule (QD). | Drug | Asciminib 80mg QD (ASAC) |
Primary outcome
Molecular Response (MR)^4.5 Rate at 48 Weeks and Difference in Rate Between Asciminib + Imatinib and Imatinib Alone
Time frame: at Week 48
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.
20 secondary outcomes
Rate of MR^4.5 at 48 Weeks (Asciminib add-on Arms vs Nilotinib)
Time frame: at Week 48
Rate of MR^4.5 by 48 Weeks (Randomized Arms)
Time frame: by 48 weeks
Rate of MR^4.5 at 96 Weeks (Randomized Arms) and Difference in Rate Between Asciminib + Imatinib and Nilotinib Alone
Time frame: at Week 96
Rate of MR^4.5 by 96 Weeks (Randomized Arms)
Time frame: by 96 weeks
Sustained MR^4.5 From at 96 Weeks (Randomized Arms)
Time frame: at 96 weeks
Time to MR^4.5 (Randomized Arms)
Time frame: 96 weeks after the last participant received the first study dose
Duration of MR^4.5 (Randomized Arms)
Time frame: 96 weeks after the last participant received the first study dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmax (Randomized Arms)
Time frame: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Tmax (Randomized Arms)
Time frame: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose; Week 4 Day 28: pre-dose (0h) 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - Cmin (Randomized Arms)
Time frame: Week 2 Day 14: pre-dose (0h), Week 4 Day 28: pre-dose (0h)
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUClast (Randomized Arms)
Time frame: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Pharmacokinetic Profile of Asciminib 40/60 mg and Imatinib When Administered in Combination - AUCtau (Randomized Arms)
Time frame: Week 2 Day 14: pre-dose (0h), 1h, 2h, 3hr 4h and 8h post-dose
Molecular Response (MR) 4.5 Rate at 48 Weeks (Asciminib Single Agent Cohort (ASAC))
Time frame: at Week 48
Time to MR^4.5 (ASAC)
Time frame: 48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Duration of MR^4.5 (ASAC)
Time frame: 48 weeks after the last enrolled participant (asciminib 80 mg cohort) received the first study dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmax (ASAC)
Time frame: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Tmax (ASAC)
Time frame: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose; Week 4 Day 28: 0h (pre-dose), 2h, 3h, 4h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - Cmin (ASAC)
Time frame: Week 2 Day 14: 0h (pre-dose), Week 4 Day 28: 0h (pre-dose)
Pharmacokinetic Profile of Asciminib 80mg QD - AUClast (ASAC)
Time frame: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose
Pharmacokinetic Profile of Asciminib 80mg QD - AUCtau (ASAC)
Time frame: Week 2 Day 14: 0h (pre-dose), 1h, 2h, 3h, 4h, 8h post-dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39696526Hughes 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.
- Individual participant dataSharing planned: Yes. 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.
Related trials for CML
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
Not yet recruitingPhase 2
Ropeginterferon Alfa-2b for the Treatment of Myelodysplastic Syndrome/Myeloproliferative Neoplasm Overlap Syndromes and Chronic Myelomonocytic Leukemia
Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
Maintenance Treatment With Imetelstat in Patients With High-Risk Myeloid Neoplasms After Allo-SCT
High-risk Myeloid Malignancy, Allogenic Stem Cell Transplantation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
30 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Asciminib add-on, Imatinib and Nilotinib in people with CML and Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 30 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Russia, Spain, Poland, United Kingdom, United States and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Molecular Response (MR)^4.5 Rate at 48 Weeks and Difference in Rate Between Asciminib + Imatinib and Imatinib Alone (time frame: at Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03578367, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026.