Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous LeukemiaPhase 2NCT04216563
ABL001 for the Treatment of Chronic Myeloid Leukemia in Patients Who Are on Therapy With Tyrosine Kinase Inhibitor
A Phase 2 study testing Asciminib in people with Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well ABL001 works in treating patients with chronic myeloid leukemia who are on therapy with tyrosine kinase inhibitor. ABL001 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia
- What is being tested?
- Asciminib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jul 2020to 17 Mar 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a diagnosis of Philadelphia chromosome (Ph)- or BCR-ABL1-positive CML (as determined by cytogenetics, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR])
- Patients should be receiving therapy with nilotinib or dasatinib, whether as initial therapy or after prior TKI, at a dose equal or lower than the standard dose
- Patients must have received TKI therapy for at least 24 months and not have required dose reductions, escalations, discontinuation or re-initiation after discontinuation of TKI in the last 6 months
- Patients must be in CCyR (by conventional karyotype or FISH, or BCR-ABL/ABL =< 1% IS if no cytogenetic analysis available within 3 months)
- Patients must have detectable BCR-ABL1 transcript levels meeting at least one of the following criteria: a. Patient has never achieved a MMR after 18 months of therapy with their current TKI, or b. Patient has not achieved MR4.5 after 36 months of therapy with their current TKI, or c. Patient has lost MMR or MR4.5 confirmed in at least two consecutive analyses separated by at least 1 month, or d. BCR-ABL1 transcript levels have reached a plateau defined as a ratio that is stable in a molecular response category (i.e., MMR, MR4 or MR4.5) in the last at least 12 months, with at least 3 values obtained during this period
- Patients must not have had a known continuous interruption of TKI therapy of greater than 14 days or for a total of 6 weeks in the 6 months prior to enrollment, unless the interruption was for an accident, unrelated hospitalization or surgical procedure, or for a treatment-free remission attempt that was unsuccessful and required re-initiation of therapy
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- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Creatinine =<1.5 x institutional upper limit of normal
- Amylase and lipase values =< 3.0 x institutional upper limit of normal
- Alkaline phosphatase =< 2.5 x institutional upper limit of normal unless considered to be not of hepatic origin
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
- Total bilirubin =< 1.5 x institutional upper limit of normal (=< 3 x upper limit of normal in patients with known Gilbert's syndrome)
- The effects of ABL001 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Women of child-bearing potential must agree to use highly effective methods of contraception during dosing and for 30 days after study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Allowable methods of birth control: 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 tubal ligation at least six weeks before the start of 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. Sexually active males must use a condom during intercourse while taking the drug and for 30 days after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
Who cannot join
- Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram or multigated acquisition (MUGA) scan
- Patients with a history of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- Corrected QT interval (QTc) of > 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval per institutional standard)
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: a. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. b. Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication
- Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
- Patients with known conditions that would significantly affect the ingestion or gastrointestinal absorption of drugs administered orally
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- Nursing women, women of childbearing potential (WOCBP) with positive blood or urine pregnancy test, or women of childbearing potential who are not willing to maintain adequate contraception
- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- Absolute neutrophil count (ANC) < 500/mm^3
- Platelet count < 50,000 mm^3
- History of other active malignancy within 2 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
- Treatment with medications that meet one of the following criteria and that cannot be discontinued 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 and/or P-glycoprotein (P-gp). Substrates of CYP3A4/5, CYP2C8, or CYP2C9 with narrow therapeutic index
- Previous treatment with or known/ suspected hypersensitivity to ABL001 or any of its excipients
- Subject has any other significant medical or psychiatric history that in the opinion of the investigator would adversely affect participation in this study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study of Dual Targeting of BCR-ABL1 by Adding the Allosteric Inhibitor ABL001 in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease (MRD) While on Therapy With Tyrosine Kinase Inhibitors
This phase II trial studies how well ABL001 works in treating patients with chronic myeloid leukemia who are on therapy with tyrosine kinase inhibitor. ABL001 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ABL001 and tyrosine kinase inhibitor together may work better than tyrosine kinase inhibitor alone in treating patients with chronic myeloid leukemia.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the clinical activity of the combination of asciminib (ABL001) and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) but detectable BCR-ABL1 transcript.
SECONDARY OBJECTIVES:
- To determine the effect of the combination of ABL001 and TKI on the rate of mismatch repair (MR)4, MR4.5, and sustained MR4.5.
II. To investigate treatment-free remission after at least 2 years of sustained deep molecular remission.
III. To determine the safety of the combination of asciminib and tyrosine kinase inhibitors.
IV. To determine the event-free survival (EFS), survival free from transformation to accelerated and blast phase (TFS), and overall survival (OS).
EXPLORATORY OBJECTIVES:
- To determine the rate of minimal residual disease (MRD) clearance using droplet digital polymerase chain reaction (ddPCR) detecting the BCR-ABL1 fusion transcript.
II. To determine the effect of therapy on quiescent leukemic Philadelphia chromosome positive (Ph+) stem cells (CFSEmax/CD34+).
III. To determine the effect of this combination on mutations in ABL1 and mutations in clonal hematopoiesis of indeterminate potential (CHIP)-associated genes using molecular barcode sequencing.
IV. To determine the effect of therapy on bone marrow progenitors in clonogenic assays.
- To describe immune effects of the combination of TKI and ABL001. VI. To describe patient reported outcomes (PRO) using the MD Anderson Symptom Inventory (MDASI)-CML instrument.
OUTLINE:
Patients receive asciminib orally (PO) twice daily (BID) for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator.
After completion of study treatment, patients are followed up every 4-8 weeks for 6 months and then every 3-6 months thereafter.
- Being tested
- Asciminib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AsciminibDrug
Also called ABL001
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (asciminib) | Experimental | Patients receive asciminib PO BID for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator. Receives: Drug: Asciminib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With a Molecular Response
Measured: At 12 months from the start of the study
Secondary outcomes (3)
Event Free Survival
Time from date of treatment start until the date of failure or death from any cause.
Measured: Up to 4 years, 7 months and 16 days
Overall Survival
Time from date of treatment start until date of death due to any cause or last Follow-up.
Measured: Up to 4 years, 7 months and 16 days
Treatment-free Remission
patients who achieved a Major Molecular response by 1.8 M from start of therapy and sustained for 27 months prior to TFR discontinuation.
Measured: Up to 4 years, 7 months and 16 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jan 2020
- Study start29 Jul 2020
- Primary completion17 Mar 2025
- Study completion17 Mar 2025
Why it stopped: 75% \< Participants, Administrativley Complete
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.
- Other trials for Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Ghayas C Issa, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04216563
- Sponsor's protocol ID
- 2019-0618
- Other IDs
- NCI-2019-08155, 2019-0618
- Status last verified
- Feb 2026
- First submitted
- 30 Dec 2019
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Dual Targeting of BCR-ABL1 by Adding the Allosteric Inhibitor ABL001 in Patients With Chronic Myeloid Leukemia (CML) and Minimal Residual Disease (MRD) While on Therapy With Tyrosine Kinase Inhibitors
- ClinicalTrials.gov ID
- NCT04216563
- Acronym / sponsor ID
- 2019-0618
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 75% \< Participants, Administrativley Complete
- Enrolment
- 7 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 29 Jul 2020 (actual)
- Primary completion
- 17 Mar 2025 (actual)
- Study completion
- 17 Mar 2025 (actual)
- First posted
- 2 Jan 2020 (actual)
- Results
- Posted 9 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well ABL001 works in treating patients with chronic myeloid leukemia who are on therapy with tyrosine kinase inhibitor. ABL001 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving ABL001 and tyrosine kinase inhibitor together may work better than tyrosine kinase inhibitor alone in treating patients with chronic myeloid leukemia.
Detailed description
PRIMARY OBJECTIVE:
- To determine the clinical activity of the combination of asciminib (ABL001) and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) but detectable BCR-ABL1 transcript.
SECONDARY OBJECTIVES:
- To determine the effect of the combination of ABL001 and TKI on the rate of mismatch repair (MR)4, MR4.5, and sustained MR4.5.
II. To investigate treatment-free remission after at least 2 years of sustained deep molecular remission.
III. To determine the safety of the combination of asciminib and tyrosine kinase inhibitors.
IV. To determine the event-free survival (EFS), survival free from transformation to accelerated and blast phase (TFS), and overall survival (OS).
EXPLORATORY OBJECTIVES:
- To determine the rate of minimal residual disease (MRD) clearance using droplet digital polymerase chain reaction (ddPCR) detecting the BCR-ABL1 fusion transcript.
II. To determine the effect of therapy on quiescent leukemic Philadelphia chromosome positive (Ph+) stem cells (CFSEmax/CD34+).
III. To determine the effect of this combination on mutations in ABL1 and mutations in clonal hematopoiesis of indeterminate potential (CHIP)-associated genes using molecular barcode sequencing.
IV. To determine the effect of therapy on bone marrow progenitors in clonogenic assays.
- To describe immune effects of the combination of TKI and ABL001. VI. To describe patient reported outcomes (PRO) using the MD Anderson Symptom Inventory (MDASI)-CML instrument.
OUTLINE:
Patients receive asciminib orally (PO) twice daily (BID) for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator.
After completion of study treatment, patients are followed up every 4-8 weeks for 6 months and then every 3-6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (asciminib) | Experimental | Drug: AsciminibPatients receive asciminib PO BID for up to 36 months while receiving standard of care dasatinib or nilotinib in the absence of disease progression or unacceptable toxicity. Patients may continue to receive asciminib after 36 months at the discretion of investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients with a diagnosis of Philadelphia chromosome (Ph)- or BCR-ABL1-positive CML (as determined by cytogenetics, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR])
- Patients should be receiving therapy with nilotinib or dasatinib, whether as initial therapy or after prior TKI, at a dose equal or lower than the standard dose
- Patients must have received TKI therapy for at least 24 months and not have required dose reductions, escalations, discontinuation or re-initiation after discontinuation of TKI in the last 6 months
- Patients must be in CCyR (by conventional karyotype or FISH, or BCR-ABL/ABL =< 1% IS if no cytogenetic analysis available within 3 months)
- Patients must have detectable BCR-ABL1 transcript levels meeting at least one of the following criteria: a. Patient has never achieved a MMR after 18 months of therapy with their current TKI, or b. Patient has not achieved MR4.5 after 36 months of therapy with their current TKI, or c. Patient has lost MMR or MR4.5 confirmed in at least two consecutive analyses separated by at least 1 month, or d. BCR-ABL1 transcript levels have reached a plateau defined as a ratio that is stable in a molecular response category (i.e., MMR, MR4 or MR4.5) in the last at least 12 months, with at least 3 values obtained during this period
Key exclusion criteria (14 listed)
- Patients with New York Heart Association (NYHA) class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) < 40% by echocardiogram or multigated acquisition (MUGA) scan
- Patients with a history of myocardial infarction within the last 6 months or unstable/uncontrolled angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias. Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third degree AV block)
- Corrected QT interval (QTc) of > 480 milliseconds (ms) on baseline electrocardiogram (ECG) (using corrected QT interval per institutional standard)
- Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: a. Risk factors for Torsades de Pointes (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. b. Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes that cannot be discontinued or replaced 7 days prior to starting study drug by safe alternative medication
- Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
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 |
|---|---|---|
| AsciminibAlso: ABL001Given PO | Drug | Treatment (asciminib) |
Primary outcome
Participants With a Molecular Response
Time frame: At 12 months from the start of the study
3 secondary outcomes
Event Free Survival
Time frame: Up to 4 years, 7 months and 16 days
Overall Survival
Time frame: Up to 4 years, 7 months and 16 days
Treatment-free Remission
Time frame: Up to 4 years, 7 months and 16 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Ghayas C Issa principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Asciminib in people with Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia, run by M.D. Anderson Cancer Center at 1 site 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 13 inclusion and 14 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: stopped early, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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 9 Jan 2026). 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?
Participants With a Molecular Response (time frame: At 12 months from the start of the study). 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 2 Mar 2026.