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Chronic Myelogenous Leukemia - Chronic PhasePhase 3AIM4CMLNCT04666259

Asciminib in Monotherapy for Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

A Phase 3 study testing ABL001 in people with Chronic Myelogenous Leukemia - Chronic Phase, run by Novartis Pharmaceuticals at 26 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study was a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ABL001
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
26 sitesUnited States
Study dates
25 May 2021to 26 Jun 2024
Phase
Phase 3
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 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants eligible for inclusion in this study must meet all of the following criteria:
  • Written informed consent must be obtained and signed prior to participation in the study
  • Male or female patients with a diagnosis of CML-CP ≥ 18 years of age
  • Patients must meet all of the following laboratory values at the screening visit:
  • < 15% blasts in peripheral blood and/or bone marrow
  • < 30% blasts plus promyelocytes in peripheral blood and/or bone marrow
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  • < 20% basophils in the peripheral blood
  • ≥ 50 x 109/L (≥ 50,000/ mm3) platelets
  • Transient prior therapy related thrombocytopenia (< 50,000/mm3 for ≤ 30 days prior to screening) is acceptable
  • No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
  • Mutation Analysis testing performed 6 months before study entry
  • Prior treatment with a minimum of:
  • 2 prior ATP-site TKIs (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of absence of T315I mutation
  • 1 prior ATP site TKI (i.e. imatinib, nilotinib, bosutinib, dasatinib or ponatinib) in case of presence of T315I mutation
  • Failure (adapted from the 2020 ELN Recommendations) or intolerance to the most recent TKI therapy at the time of screening
  • Failure for CML-CP patients (CP at the time of initiation of last therapy) is defined as meeting at least one of the following criteria.
  • Three months after the initiation of therapy: >10% BCR-ABL1 on International Scale (IS) if confirmed within 1-3 months
  • Six months after the initiation of therapy: BCR-ABL1 ratio > 10% IS
  • Twelve months after initiation of therapy: BCR-ABL1 ratio > 1% IS
  • At any time after the initiation of therapy, loss of CHR, MR2
  • At any time after the initiation of therapy, the development of new BCR-ABL1 mutations which potentially cause resistance to current treatment
  • At any time 12 months after the initiation of therapy, BCR-ABL1 ratio ≥ 1% IS or loss of MMR
  • At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: CCA/Ph+
  • Intolerance is defined as:
  • Non-hematologic intolerance: Patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
  • Hematologic intolerance: Patients with grade 3 or 4 toxicity (absolute neutrophil count [ANC] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended by manufacturer
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  • Evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening which are amenable to standardized RQ-PCR quantification.
  • Adequate end organ function, within 12 days before the first dose of asciminib treatment. Patients with mild to moderate renal and hepatic impairment are eligible if:
  • Total bilirubin ≤ 3.0 x ULN without AST/ALT increase
  • Aspartate transaminase (AST) ≤ 5.0 x ULN
  • Alanine transaminase (ALT) ≤ 5.0 x ULN
  • Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN - ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Creatinine clearance ≥ 30 mL/min as calculated using Cockcroft-Gault formula
  • Patients must avoid consumption of grapefruit, Seville oranges or products containing the juice of each during the entire study and preferably 7 days before the first dose of study medications, due to potential CYP3A4 interaction with the study medications. Orange juice is allowed.
  • Treatment with medications that meet one of the following criteria is allowed if used with caution at least one week prior to the start of treatment with study treatment:
  • Moderate or strong inducers of CYP3A
  • Moderate or strong inhibitors of CYP3A
  • Patients must have the following electrolyte values (as per central laboratory tests) within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication:
  • Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)
  • Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)
  • Magnesium, with the exception of magnesium increase > ULN - 3.0 mg/dL; > ULN - 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits.

Who cannot join

  • Patients eligible for this study must not meet any of the following criteria:
  • Known second chronic phase of CML after previous progression to AP/BC
  • Previous treatment with a hematopoietic stem-cell transplantation
  • Cardiac or cardiac repolarization abnormality, including any of the following:
  • History within 6 months prior to starting study treatment of myocardial infarction (MI), angina pectoris, coronary artery bypass graft (CABG)
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)
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  • QTcF at screening ≥450 msec (male patients), ≥460 msec (female patients)
  • 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 (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
  • Concomitant medication(s) with a "Known risk of Torsades de Pointes" per wwwcrediblemeds.org/ that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication.
  • Inability to determine the QTcF interval
  • 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, pulmonary hypertension)
  • History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
  • Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
  • History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
  • Previous treatment with or known/ suspected hypersensitivity to asciminib or any of its excipients.
  • Participation in a prior investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is longer
  • Pregnant or nursing (lactating) women
  • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception.
  • Highly effective contraception methods include:
  • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
  • Female sterilization (have had surgical bilateral oophorectomy (with or without hysterectomy) total hysterectomy or bilateral tubal ligation at least six weeks before taking study treatment). In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
  • Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.
  • Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception.
  • In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.
  • Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before taking study medication. In the case of oophorectomy alone, women are considered post-menopausal and not of child bearing potential only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 3 days after stopping study (only for patients treated with asciminib). A condom is required for all sexually active male participants on asciminib treatment to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, these male participants must not donate sperm for the time period specified above.
  • If a patient is presenting with symptoms suggestive of possible COVID-19 infection, we advise ruling it out by appropriate testing recommended by health authorities.
  • Nucleic acid amplification tests for viral RNA (polymerase chain reaction), in order to measure current infection with SARS-CoV-2
  • Antigen tests for rapid detection of SARS-CoV-2
  • Antibody (serology) tests to detect the presence of antibodies to SARS-CoV-2

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

United States26 sites
  • Alaska Oncology and Hematology

    Anchorage, Alaska, 99508

  • Michigan Med University of Michigan

    Ann Arbor, Michigan, 48109 5271

  • Indiana Blood and Marrow Institute

    Beech Grove, Indiana, 46107

  • Rocky Mountain Cancer Centers

    Boulder, Colorado, 80304

  • Uni of Cincinnati Medical Center

    Cincinnati, Ohio, 45219

  • Oncology Hematology Care Inc

    Cincinnati, Ohio, 45242

  • Texas Oncology

    Dallas, Texas, 75251

  • Texas Oncology P A

    Fort Worth, Texas, 76104

  • Memorial Cancer Institute

    Hollywood, Florida, 33021

  • Univ of TX MD Anderson Cancer Cntr

    Houston, Texas, 77030

  • University of Kentucky

    Lexington, Kentucky, 40536

  • Pacific Shores Medical Group

    Long Beach, California, 90813

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • Arizona Oncology Associates

    Phoenix, Arizona, 85016

  • Cancer Treatment Centers of America

    Phoenix, Arizona, 85027

  • Northwest Cancer Specialists

    Portland, Oregon, 97210

  • Florida Cancer Specialists

    Sarasota, Florida, 34232

  • Siteman Cancer Center

    St Louis, Missouri, 63110

  • Florida Cancer Specialists-North

    St. Petersburg, Florida, 33705

  • Florida Cancer Specialists East

    Stuart, Florida, 34994

  • Florida Cancer Specialists Pan

    Tallahassee, Florida, 32308

  • Lundquist Inst BioMed at Harbor

    Torrance, California, 90509-2910

  • Texas Oncology Northeast Texas

    Tyler, Texas, 75702

  • Wake Forest University Baptist Medical Center

    Winston-Salem, North Carolina, 27157

  • Uni of Massachusetts Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: An Open Label, Multi-center Phase IIIb Study of Asciminib (ABL001) Monotherapy in Previously Treated Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) With and Without T315I Mutation

This study was a multicenter Phase IIIb open-label, three-cohort study of asciminib in patients with CML-CP without T315I mutation who have had at least 2 prior TKIs and CML-CP harboring the T315I mutation with at least 1 prior TKI

Read the detailed description

This trial consisted of three periods: screening and baseline for up to 21 days, active treatment for up to 72 weeks and a safety follow up period for 30 days.

One hundred and fifteen (115) patients with chronic myeloid leukemia in chronic phase (CML-CP) without T315I mutation who have had at least 2 prior Tyrosine Kinase Inhibitors (TKIs) and CML-CP with the T315I mutation with at least 1 prior TKI were planned for this study, however the study was finally completed with 56 participants due to enrollment issues.

Informed consent was obtained before any procedures were performed for the study including eligibility assessments. The results of the real time quantitative polymerase chain reaction (RQ-PCR) must be available prior to randomization and first dose of study treatment.

Patients with CML-CP without T315I mutation were randomly assigned to either cohort A or B. Patients with the T315I mutation were enrolled in cohort C. During treatment period asciminib was taken orally: Cohort A was administered 40 mg twice a day, Cohort B was administered 80 mg once a day and Cohort C was administered 200 mg twice a day. The patients were treated up to end of study treatment period defined as up to 72 weeks after the last patient receives the first dose. Patients may have been discontinued from treatment with the study drug at any time due to unacceptable toxicity, disease progression and/or at the discretion of the investigator or the patient.

Being tested
ABL001
Keywords
CML, T315I mutation, CP, Asciminib,, BCR-ABL,, ABL001,, CML-AP,, ELN, MMR, Molecular Response, MR4.5, MR4, RQ-PCR, AIM4CML,, tyrosine Kinase Inhibitor, TKI, adult
Medical subject headings
Leukemia, Myeloid, Chronic-Phase

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABL001Drug

    Asciminib will be supplied as 20 mg or 40 mg strength tablets will be administered orally in accordance with the assigned cohort.

Study groups in NCT04666259
Study groupRoleWhat they receive
Cohort AExperimental40 mg asciminib orally twice daily (BID)
Receives: Drug: ABL001
Cohort BExperimental80 mg asciminib orally once daily (QD)
Receives: Drug: ABL001
Cohort CExperimental200 mg asciminib orally twice daily (BID)
Receives: Drug: ABL001

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A and B up to 24 Weeks

    Adverse events (AEs) and serious adverse events (SAEs) are summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) are reported as adverse events and or serious adverse events as determined by the investigator.

    Measured: Baseline to up to 24 Weeks

Secondary outcomes (11)
  1. Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A, B and C by Week 48

    Adverse events (AEs) and serious adverse events (SAEs) were summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) were reported as adverse events and or serious adverse events as determined by the investigator.

    Measured: Baseline up to 48 weeks

  2. Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A, B and C by Week 72

    Adverse events (AEs) and serious adverse events (SAEs) were summarized by cohort. Clinically significant findings for vitals, laboratory values and electrocardiogram (ECG) were reported as adverse events and or serious adverse events as determined by the investigator.

    Measured: Baseline up to 72 weeks

  3. Percentage of Patients Achieving Complete Hematologic Response (CHR) for Cohorts A, B and C

    A complete hematologic response (CHR) is defined as all of the following present for ≥ 4 weeks:

    • White blood cell count (WBC) <10 x 10^9/L
    • Platelet count <450 x 10^9/L
    • Basophils <5%,
    • No blasts and promyelocytes in peripheral blood
    • Myelocytes + metamyelocytes < 5% in peripheral blood
    • No evidence of extramedullary disease, including spleen and liver

    The estimated cumulative incidence rates were presented.

    Measured: Baseline to 12, 24, 48, 72 weeks

  4. Percentage of Patients Achieving Major Molecular Response (MMR) for Cohorts A, B and C

    The rate of major molecular response (MMR) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 3 log reduction of BCR-ABL (transcript from standardized baseline or ≤0.1% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome.

    The estimated cumulative incidence rates were presented.

    Measured: Baseline up to 12, 24, 48, 72 weeks

  5. Percentage of Patients Achieving Molecular Response (MR2) for Cohorts A, B and C

    The rate of molecular response (MR2) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 2 log reduction of BCR-ABL (transcript from standardized baseline or ≤ 1% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome.

    The estimated cumulative incidence rates were presented.

    Measured: Baseline up to 12, 24, 48, 72 weeks

  6. Percentage of Patients Achieving Molecular Response 4 (MR4) for Cohorts A, B and C

    The rate of molecular response (MR4) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 4 log reduction of BCR-ABL (transcript from standardized baseline or ≤ 0.01% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome.

    The estimated cumulative incidence rates were presented.

    Measured: Baseline up to 12, 24, 48, 72 weeks

  7. Percentage of Patients Achieving Molecular Response 4.5 (MR4.5) for Cohorts A, B and C

    The rate of molecular response (MR4.5) by 12, 24, 48 and 72 weeks after the start of first study medication is defined as ≥ 4.5 log reduction of BCR-ABL (transcript from standardized baseline or ≤ 0.0032% BCR-ABL/ABL % by international scale, measured by real-time quantitative polymerase chain reaction (RQ-PCR). BCR-ABL fusion gene is also called the Philadelphia chromosome.

    The estimated cumulative incidence rates were presented.

    Measured: Baseline up to 12, 24, 48, 72 weeks

  8. Time to Achieve CHR, MR2, MMR, MR4, MR4.5 for Cohorts A, B and C

    Time to achieving a response level is defined as the time from the date of the first dose of study medication to the first documented achievement of each defined response level. Time to achieve a specific response level was analyzed using the Kaplan-Meier Product-Limit method. Patients who are known to be without achieving that response level were censored at the last adequate assessment.

    Measured: Baseline up to 72 weeks

  9. Duration of CHR, MR2, MMR, MR4 and MR4.5 for Cohorts A, B and C

    Duration of Response (DOR) is the time from the date of the first documented molecular response level to the date of first documented loss of the response level or death due to any cause, whichever occurs first. DOR for each response level was analyzed using the Kaplan-Meier Product-Limit method. Participants continuing without that event were censored at the date of their last adequate response assessment.

    Measured: Baseline up 72 weeks

  10. Progression Free Survival (PFS) for Cohorts A, B and C

    Progression Free Survival (PFS) is defined as time from the first dose of study medication to disease progression to accelerated phase/blast crisis (AP/BC) or death due to any cause, whichever occurs first. PFS was analyzed using the Kaplan-Meier Product-Limit method. Subjects who did not progress were censored at the last adequate assessment.

    Measured: Baseline up to 72 weeks

  11. Overall Survival Overall Survival (OS) for Cohorts A, B and C

    Overall Survival (OS) is defined as the time from the first dose of study medication to death due to any cause during study. If a patient was not known to have died, then OS was censored at the latest date the patient was known to be alive. OS was analyzed using the Kaplan-Meier Product-Limit method

    Measured: Baseline up to 72 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2020
  2. Study start25 May 2021
  3. Primary completion20 Jun 2023
  4. Study completion26 Jun 2024

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04666259
Sponsor's protocol ID
CABL001AUS04
Acronym
AIM4CML
Status last verified
Oct 2025
First submitted
7 Dec 2020
Last updated
16 Oct 2025
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 review 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 availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ABL001 in people with Chronic Myelogenous Leukemia - Chronic Phase, run by Novartis Pharmaceuticals at 26 sites in United States.

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 43 inclusion and 32 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 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 12 Jul 2024). 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?

Number of Participants With Adverse Events and Serious Adverse Events for Cohorts A and B up to 24 Weeks (time frame: Baseline to up to 24 Weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 16 Oct 2025.

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