Chronic Myeloid LeukemiaPhase 2CMLXINCT03906292
Frontline Asciminib Combination in Chronic Phase CML
A Phase 2 study testing Imatinib, Nilotinib 300 mg and Dasatinib in people with Chronic Myeloid Leukemia, run by University of Jena at 21 sites in Germany.
Trial summary
Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Imatinib, Nilotinib 300 mg and Dasatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 21 sitesGermany
- Study dates
- 19 Aug 2019to Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of the Ph+ chromosome [t(9;22)(q34;q11)].
- Ph-negative cases or patients with variant translocations who are BCR-ABL1 positive in multiplex PCR 35 will be also considered eligible.
- ECOG performance status of ≤2.
- Age ≥ 18 years old (no upper age limit is given)
- Serum levels of potassium, magnesium, total calcium within the normal limits (≥LLN [lower limit of normal] and ≤ULN [upper limit of normal]). Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
- AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
Show all 10Show fewer
- Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
- Total bilirubin ≤1.5 x ULN, except known Gilbert disease
- Serum creatinine ≤2 x ULN
- Written informed consent prior to any study procedures being performed.
Who cannot join
- Allogeneic stem cell transplantation
- Known impaired cardiac function, including any of the following:
- Congenital long QT syndrome
- History of or presence of clinically significant ventricular or atrial tachyarrhythmia
- QTc >450 msec on screening ECG
- Myocardial infarction within 12 months prior to starting therapy
Show all 17Show fewer
- Other clinical significant heart disease (e.g. unstable angina, congestive heart failure)
- Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores >6), even if controlled
- Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
- Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
- Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
- Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Patients who are pregnant or breastfeeding or women of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study start. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Male and female patients must agree to employ an effective method of birth control throughout the study and for up to 2 weeks following discontinuation of study drug
- Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
- Known serious hypersensitivity reactions to asciminib, imatinib, nilotinib or dasatinib
- Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
- Patients unwilling or unable to comply with the protocol.
Trial locations and contacts
21 sites in 1 country.
21 sites in 1 country
Germany21 sites
Universitätsklinikum Aachen Medizinische Klinik IV
Aachen, 52074
Charite Universitätsmeditin Berlin, Campus Virchow Klinikum
Berlin, 13353
Universitätsklinikum Bonn
Bonn, 53105
Klinikum Bremen Mitte
Bremen, 28177
Klinikum Chemnitz gGmbH
Chemnitz, 09113
GOKOS GmbH
Dresden, 01307
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, 01307
Universitätsklinikum Erlangen
Erlangen, 91054
Universitätsklinikum Essen
Essen, 45122
Universitätsklinikum Frankfurt
Frankfurt, 60590
Universitätsklinikum Freiburg
Freiburg im Breisgau, 79106
Universitätsklinikum Jena
Jena, 07747
Universitätsklinikum Leipzig
Leipzig, 04103
Gemeinschaftspraxis Dres. Müller/ Kröning/ Jentsch-Ullrich/ Tietze/ Krogel
Magdeburg, 39104
Universitätsmedizin der Johannes- Gutenberg Universität Mainz
Mainz, 55131
Universitätsmedizin Mannheim
Mannheim, 68169
Universitätsklinikum Gießen und Marburg
Marburg, 35043
Klinikum rechts der Isar
München, 81675
Brüderkrankenhaus St. Josef Paderborn
Paderborn, 33098
Krankenhaus Barmherzige Brüder Regensburg
Regensburg, 93049
Universitätsklinikum Ulm
Ulm, 89081
About this study
Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.
Read the detailed description
Despite the dramatic progress made over the past decade with TKIs in the treatment of CML, allogeneic stem cell transplant remains the only proven curative therapy. To achieve cure or benefit from treatment-free remissions with pharmacologically-based therapies, it is estimated that patients will likely need to achieve a sustained reduction in tumor burden corresponding to a deep molecular response of at least 4 logs (MR4). Currently, only 30.8% of patients achieve a deep molecular response after 12 months of treatment with single agent nilotinib.
The development of the novel and potent BCR-ABL1 allosteric inhibitor, asciminib, presents an opportunity to assess the effect of a different mechanism of inhibition of BCR-ABL1 in the first-line treatment of CML to enhance speed of response and to increase the patient population benefitting from deep molecular response. Dosing a combination of asciminib with an ATP-site inhibitor also has the potential to prevent the emergence of resistance due to point mutations being acquired in one of the binding sites.
The safety, tolerability and pharmacokinetic profile of asciminib as a single agent and in combination with either nilotinib or imatinib or dasatinib was assessed in a phase-I study. At the doses chosen here, all three combination treatments were well tolerated.
Since in all patient cohorts the standard of care therapy will remain the backbone of initial therapy, there is no reason to expect an efficacy problem with the combination therapies.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Imatinib, Nilotinib 300 mg, Dasatinib, Asciminib
- 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.
ImatinibDrug
Also called Imatinib 400 mg QD and asciminib 60 mg QD
Imatinib 400 mg QD and asciminib 60 mg QD
Nilotinib 300 mgDrug
Also called Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD
Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD
DasatinibDrug
Also called Dasatinib 100 mg QD and asciminib 80 mg QD
Dasatinib 100 mg QD and asciminib 80 mg QD
AsciminibDrug
Asciminib 80 mg QD Monotherapy
| Study group | Role | What they receive |
|---|---|---|
| Asciminib 60mg QD | Experimental | Standard therapy of Imatinib 400 mg QD and asciminib 60 mg QD Receives: Drug: Imatinib; Drug: Asciminib |
| Asciminb 20 mg BID | Experimental | Standard therapy of Nilotinib 300 mg BID and asciminib 20 mg BID Receives: Drug: Nilotinib 300 mg; Drug: Asciminib |
| Asciminib 40 mg QD | Experimental | Standard therapy of Nilotinib 300 mg BID and asciminib 40 mg QD Receives: Drug: Nilotinib 300 mg; Drug: Asciminib |
| Asciminib 80 mg QD | Experimental | Standard therapy of Dasatinib 100 mg QD and asciminib 80 mg QD Receives: Drug: Dasatinib; Drug: Asciminib |
| Asciminib 80 mg QD monotherapy | Experimental | Asciminib 80 mg QD as a single agent Receives: Drug: Asciminib |
What is being measured
The primary outcome is the main question the study is designed to answer.
deep molecular response (Rate of MR4)
Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels
Measured: at month 12 after Start of Standard-Therapy
deep molecular Response (Rate of MR4.5)
Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels
Measured: at month 36 after Start of Standard-Therapy
Secondary outcomes (6)
molecular response (MMR and MR4.5)
Achievement of deep molecular response throught standardized testing of BCR-ABL-transcript levels
Measured: at and by 6, 12, 18, 24, 36 and 60 months after Start of Therapy
Adverse Events
Incidence of adverse events grade 1-5 and 3-5
Measured: at and by baseline, 3, 6, 12, 15, 18, 21, 24, 36 and 60 months after Start of Therapy
Progression free survival
Progression free survival at the end of the study
Measured: at month 60 after Start of Therapy
Overall survival
Overall survival at the end of the study
Measured: at month 60 after Start of Therapy
Maintenance of MR4.5 during Asciminib-monotherapy
Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels
Measured: at month 36 and 60 after Start of Therapy
Achievement and durability of treatment-free remission
Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels
Measured: months 37 and 60 after Start of Therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start19 Aug 2019
- Primary completionMar 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- 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
- Model description
- 5 parallel cohorts
- Masking
- None (open label)
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Jena
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Thomas Ernst, PD Dr. med., University of Jena
- Investigators
- Thomas Ernst, Prof. Dr., Principal investigator, University Hospital Jena
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906292
- Sponsor's protocol ID
- Fascination
- Other IDs
- 2024-516212-24-00
- Acronym
- CMLXI
- Status last verified
- Aug 2026
- First submitted
- 14 Dec 2018
- Last updated
- 18 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frontline Asciminib Combination in Chronic Phase CML
- ClinicalTrials.gov ID
- NCT03906292
- Acronym / sponsor ID
- CMLXI / Fascination
- Conditions
- Chronic Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 125 participants (actual)
- Lead sponsor
- University of JenaUniversity, hospital or other
- Collaborators
- Ludwig-Maximilians - University of Munich, Novartis Pharmaceuticals
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 8 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.
Detailed description
Despite the dramatic progress made over the past decade with TKIs in the treatment of CML, allogeneic stem cell transplant remains the only proven curative therapy. To achieve cure or benefit from treatment-free remissions with pharmacologically-based therapies, it is estimated that patients will likely need to achieve a sustained reduction in tumor burden corresponding to a deep molecular response of at least 4 logs (MR4). Currently, only 30.8% of patients achieve a deep molecular response after 12 months of treatment with single agent nilotinib.
The development of the novel and potent BCR-ABL1 allosteric inhibitor, asciminib, presents an opportunity to assess the effect of a different mechanism of inhibition of BCR-ABL1 in the first-line treatment of CML to enhance speed of response and to increase the patient population benefitting from deep molecular response. Dosing a combination of asciminib with an ATP-site inhibitor also has the potential to prevent the emergence of resistance due to point mutations being acquired in one of the binding sites.
The safety, tolerability and pharmacokinetic profile of asciminib as a single agent and in combination with either nilotinib or imatinib or dasatinib was assessed in a phase-I study. At the doses chosen here, all three combination treatments were well tolerated.
Since in all patient cohorts the standard of care therapy will remain the backbone of initial therapy, there is no reason to expect an efficacy problem with the combination therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
- Model description
- 5 parallel cohorts
| Arm | Type | Receives |
|---|---|---|
| Asciminib 60mg QD | Experimental | Drug: Imatinib, Drug: AsciminibStandard therapy of Imatinib 400 mg QD and asciminib 60 mg QD |
| Asciminb 20 mg BID | Experimental | Drug: Nilotinib 300 mg, Drug: AsciminibStandard therapy of Nilotinib 300 mg BID and asciminib 20 mg BID |
| Asciminib 40 mg QD | Experimental | Drug: Nilotinib 300 mg, Drug: AsciminibStandard therapy of Nilotinib 300 mg BID and asciminib 40 mg QD |
| Asciminib 80 mg QD | Experimental | Drug: Dasatinib, Drug: AsciminibStandard therapy of Dasatinib 100 mg QD and asciminib 80 mg QD |
| Asciminib 80 mg QD monotherapy | Experimental | Drug: AsciminibAsciminib 80 mg QD as a single agent |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of the Ph+ chromosome [t(9;22)(q34;q11)].
- Ph-negative cases or patients with variant translocations who are BCR-ABL1 positive in multiplex PCR 35 will be also considered eligible.
- ECOG performance status of ≤2.
- Age ≥ 18 years old (no upper age limit is given)
- Serum levels of potassium, magnesium, total calcium within the normal limits (≥LLN [lower limit of normal] and ≤ULN [upper limit of normal]). Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
Key exclusion criteria (17 listed)
- Allogeneic stem cell transplantation
- Known impaired cardiac function, including any of the following:
- Other clinical significant heart disease (e.g. unstable angina, congestive heart failure)
- Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores >6), even if controlled
- Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
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 |
|---|---|---|
| ImatinibAlso: Imatinib 400 mg QD and asciminib 60 mg QDImatinib 400 mg QD and asciminib 60 mg QD | Drug | Asciminib 60mg QD |
| Nilotinib 300 mgAlso: Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QDNilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD | Drug | Asciminb 20 mg BID, Asciminib 40 mg QD |
| DasatinibAlso: Dasatinib 100 mg QD and asciminib 80 mg QDDasatinib 100 mg QD and asciminib 80 mg QD | Drug | Asciminib 80 mg QD |
| AsciminibAsciminib 80 mg QD Monotherapy | Drug | Asciminb 20 mg BID, Asciminib 40 mg QD, Asciminib 60mg QD, Asciminib 80 mg QD, Asciminib 80 mg QD monotherapy |
Primary outcome
deep molecular response (Rate of MR4)
Time frame: at month 12 after Start of Standard-Therapy
Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels
deep molecular Response (Rate of MR4.5)
Time frame: at month 36 after Start of Standard-Therapy
Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels
6 secondary outcomes
molecular response (MMR and MR4.5)
Time frame: at and by 6, 12, 18, 24, 36 and 60 months after Start of Therapy
Adverse Events
Time frame: at and by baseline, 3, 6, 12, 15, 18, 21, 24, 36 and 60 months after Start of Therapy
Progression free survival
Time frame: at month 60 after Start of Therapy
Overall survival
Time frame: at month 60 after Start of Therapy
Maintenance of MR4.5 during Asciminib-monotherapy
Time frame: at month 36 and 60 after Start of Therapy
Achievement and durability of treatment-free remission
Time frame: months 37 and 60 after Start of Therapy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2026.
- Individual participant dataSharing planned: No
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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.
Thomas Ernst, Prof. Dr. principal investigator
University Hospital Jena
21 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Imatinib, Nilotinib 300 mg and Dasatinib in people with Chronic Myeloid Leukemia, run by University of Jena at 21 sites in Germany.
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 10 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Germany. 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?
This study is still under way. Results are not available in the source record yet.
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?
deep molecular response (Rate of MR4) (time frame: at month 12 after Start of Standard-Therapy). The study lists 2 primary outcomes in all. 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 18 Aug 2026.