Chronic Myeloid Leukemia (CML) inPhase 2NCT07538401
ASCiminib, With or Without Dasatinib Combination, as a 2nd-Line Therapy to ADVANCE the Treatment for Chronic Myelogenous Leukemia in Chronic Phase (ASC2ADVANCE)
A Phase 2 study testing No high risk mutation and High Risk Mutation in people with Chronic Myeloid Leukemia (CML) in, run by University Health Network, Toronto.
Trial summary
This study is testing a new way to treat people with a type of blood cancer called chronic myeloid leukemia (CML) in chronic phase. This study is for the patients whose first treatment with a drug called a tyrosine kinase inhibitor (TKI; standard therapy) did not work well and resistant to the TKI drug. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia (CML) in
- What is being tested?
- No high risk mutation and High Risk Mutation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- No sites listed yet
- Study dates
- 25 Apr 2026to 25 Apr 2029
- Phase
- Phase 2
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients ≥18 years of age
- Diagnosis of CML in chronic phase as per WHO criteria based on the presence of BCR::ABL1 fusion gene by PCR at original diagnosis. Confirmation is recommended, if possible, by demonstrating the Philadelphia chromosome or variants by cytogenetics or FISH (Fluorescence In Situ Hybridization) in addition to bone marrow morphology confirming CML-CP. Patients with additional chromosomal abnormalities in addition to the Philadelphia chromosome are eligible. NGS testing at initial diagnosis is not required.
- Warning or failure to first line of TKI therapy at the time of screening due to resistance or suboptimal response (based on the ELN 2020 failure criteria)
- BCR::ABL1 transcript type is trackable with institutional RQ-PCR (Real-time Quantitative Polymerase Chain Reaction) testing for response assessment
- No prior or concurrent malignancies, except for adequately treated non-melanoma skin cancer, cervical carcinoma-in-situ, adequately treated Stage I or II cancer from which patient is in complete remission, or any other cancer from which patient has been disease free for a minimum of five years
- Patients must be ASC naïve
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- Agree to conduct somatic mutation profile testing at enrollment
- Adequate organ function defined by:
- Creatinine clearance level ≥ 30 mL/min as calculated using the Cockcroft-Gault formula
- Total bilirubin (TBL) ≤ 3.0 ULN without AST/ALT increase; participants with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤1.5 x ULN
- Aspartate transaminase (AST) ≤ 5.0 x ULN
- Alanine transaminase (ALT) ≤ 5.0 x ULN
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN
- Serum lipase ≤ 1.5 x ULN. For serum lipase > ULN and ≤ 1.5 x ULN, value should be considered not clinically significant and not associated with risk factors for acute pancreatitis
- Women of childbearing potential (defined as all women physiologically capable of becoming pregnant) and fertile men must agree to use adequate contraception from the time of signing the informed consent form and for at least 7 days following the last dose of study treatment. Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e., age, history of vasomotor symptoms). Acceptable methods of contraception include the following (applicable to the patient and/or patient's partner(s)):
- Total abstinence
- 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 the case of oral contraception use, women should have been stable on the same pill for a minimum of 3 months before taking study drug.
- 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). A vasectomized male partner should be the sole partner for that patient.
Who cannot join
- Failure to provide informed consent
- Prior stem cell or bone marrow transplant
- Previous diagnosis of CML in accelerated phase (AP) or blast crisis (BC)
- Known second chronic phase of CML after previous progression to AP/BC
- ECOG performance status ≥3.
- Any one of the following cardiac symptoms:
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- History of myocardial infarction (MI), coronary artery bypass graft (CABG) surgery, or coronary stent placement within the past six months
- Uncontrolled angina or uncontrolled congestive heart failure (NYHA class III or IV) within the past six months.
- Diagnosed congenital long QT syndrome
- Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
- Clinically significant, uncontrolled atrial fibrillation or other clinically relevant arrhythmias requiring ongoing intervention.
- Prolonged QTc interval on pre-entry electrocardiogram. Specifically, QTcF and QTc ≥ 450ms for male patients or ≥ 460ms for female patients. To be reported as the average of three serial baseline ECGs (using the QTcF formula) as determined by central reading. If QTcF ≥ 450 ms and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient rescreened for QTc.
- Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to DAS administration.
- Concurrent medical condition, which may increase the risk of toxicity including but not limited to: Pleural or pericardial effusion of any grade and pulmonary arterial hypertension.
- History of significant bleeding disorder unrelated to cancer, including any of the following:
- Diagnosed congenital bleeding disorder (e.g., von Willebrand's disease)
- Diagnosed acquired bleeding disorder within one year (e.g., acquired antifactor VIII antibodies).
- Ongoing or recent (≤ 3 months) significant gastrointestinal bleeding
- Presence of ASC resistant ABL1 KDM (Myristolyate site mutation, T315I, M244V, V299L, F359) using institutional Sanger sequencing test in each center as a SOC (if the ABL1 KDM result is available).
- History of first line TKI discontinuation (with optimal response) due to adverse events including hematologic or non-hematologic toxicities
- History of recurrent or chronic pancreatitis
- Treatment with strong inducers of CYP3A is not allowed and should be switched to an alternative at least one week prior to the start of study treatment
- Pregnant or nursing (lactating) women
- Participation in a prior investigational study within 30 days prior to enrolment, or within 5 half-lives of the investigational product, whichever is longer.
- Known central nervous system infiltration (in absence of suspicion of CNS involvement, lumbar puncture not required).
- Known history of chronic Hepatitis B (HBV), or chronic Hepatitis C (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBc Ab/anti HBc) will be performed at screening. If anti-HBc is positive, HBV-DNA evaluation must be carried out at screening. Patients having positive HBV-DNA or positive HBsAg must not be enrolled in the study.
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Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
This study is testing a new way to treat people with a type of blood cancer called chronic myeloid leukemia (CML) in chronic phase.
This study is for the patients whose first treatment with a drug called a tyrosine kinase inhibitor (TKI; standard therapy) did not work well and resistant to the TKI drug. The study is checking if a drug called Asciminib (having different way of action), used either by itself or with another drug called Dasatinib, can be a better second option to help control the CML.
- Conditions
- Chronic Myeloid Leukemia (CML) in
- Being tested
- No high risk mutation, High Risk Mutation
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No high risk mutationDrug
No HighRisk-Patients without a high-risk mutation profile will receive ASC monotherapy at a dose of 80 mg daily, in 28-day cycles, administered every 4 weeks.
High Risk MutationDrug
Patients with a high-risk mutation profile will receive ASC 80 mg daily for the first 4 weeks (Cycle 1), followed by a combination of ASC 80 mg + DAS 100 mg daily starting from Cycle 2 onward.
| Study group | Role | What they receive |
|---|---|---|
| No high risk mutation | Experimental | Patients without a high-risk mutation profile will receive ASC monotherapy at a dose of 80 mg daily, in 28-day cycles, administered every 4 weeks. Receives: Drug: No high risk mutation |
| High Risk Mutation | Experimental | Patients with a high-risk mutation profile will receive ASC 80 mg daily for the first 4 weeks (Cycle 1), followed by a combination of ASC 80 mg + DAS 100 mg daily starting from Cycle 2 onward. Receives: Drug: High Risk Mutation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcome will be the proportion of patients achieving MMR, defined as a 3-log reduction or deeper (0.1% International Scale), after 24 weeks (6 cycles) of treatment with ASC as a second-line therapy.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
25 Apr 202625 Apr 2029
- First posted20 Apr 2026
- Study start25 Apr 2026 (estimated)
- Primary completion25 Apr 2028 (estimated)
- Study completion25 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid Leukemia (CML) inStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07538401
- Sponsor's protocol ID
- ASC2Advance
- Other IDs
- OZUHN-044
- Status last verified
- Mar 2026
- First submitted
- 5 Mar 2026
- Last updated
- 20 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No