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Active, not recruitingNCT03906292CMLXIUpdated Aug 18, 2026

Frontline Asciminib Combination in Chronic Phase CML

A Phase 2 interventional study of Imatinib and Nilotinib 300 mg in Chronic Myeloid Leukemia, sponsored by University of Jena. Active, not recruiting at 21 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-18.

Sponsored by University of Jena · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
125
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Chronic Myeloid Leukemia
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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
  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
125 participants (actual)

Study arms

  • Experimental
    Asciminib 60mg QD

    Standard therapy of Imatinib 400 mg QD and asciminib 60 mg QD

    Drug: Imatinib · Drug: Asciminib

  • Experimental
    Asciminb 20 mg BID

    Standard therapy of Nilotinib 300 mg BID and asciminib 20 mg BID

    Drug: Nilotinib 300 mg · Drug: Asciminib

  • Experimental
    Asciminib 40 mg QD

    Standard therapy of Nilotinib 300 mg BID and asciminib 40 mg QD

    Drug: Nilotinib 300 mg · Drug: Asciminib

  • Experimental
    Asciminib 80 mg QD

    Standard therapy of Dasatinib 100 mg QD and asciminib 80 mg QD

    Drug: Dasatinib · Drug: Asciminib

  • Experimental
    Asciminib 80 mg QD monotherapy

    Asciminib 80 mg QD as a single agent

    Drug: Asciminib

Interventions

  • DrugImatinib

    Imatinib 400 mg QD and asciminib 60 mg QD

    Also known as: Imatinib 400 mg QD and asciminib 60 mg QD

  • DrugNilotinib 300 mg

    Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD

    Also known as: Nilotinib 300 mg BID and asciminib 20 mg BID or 40 mg QD

  • DrugDasatinib

    Dasatinib 100 mg QD and asciminib 80 mg QD

    Also known as: Dasatinib 100 mg QD and asciminib 80 mg QD

  • DrugAsciminib

    Asciminib 80 mg QD Monotherapy

05

What researchers measure

Primary outcomes

  1. deep molecular response (Rate of MR4)

    Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels

    Time frame: at month 12 after Start of Standard-Therapy

  2. deep molecular Response (Rate of MR4.5)

    Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels

    Time frame: at month 36 after Start of Standard-Therapy

Secondary outcomes

  1. molecular response (MMR and MR4.5)

    Achievement of deep molecular response throught standardized testing of BCR-ABL-transcript levels

    Time frame: at and by 6, 12, 18, 24, 36 and 60 months after Start of Therapy

  2. Adverse Events

    Incidence of adverse events grade 1-5 and 3-5

    Time frame: at and by baseline, 3, 6, 12, 15, 18, 21, 24, 36 and 60 months after Start of Therapy

  3. Progression free survival

    Progression free survival at the end of the study

    Time frame: at month 60 after Start of Therapy

  4. Overall survival

    Overall survival at the end of the study

    Time frame: at month 60 after Start of Therapy

  5. Maintenance of MR4.5 during Asciminib-monotherapy

    Achievement of deep molecular response (MR4.5) throught standardized testing of BCR-ABL-transcript Levels

    Time frame: at month 36 and 60 after Start of Therapy

  6. Achievement and durability of treatment-free remission

    Achievement of deep molecular response (MR4) throught standardized testing of BCR-ABL-transcript Levels

    Time frame: months 37 and 60 after Start of Therapy

06

Study locations

21 sites
  • Universitätsklinikum Aachen Medizinische Klinik IV
    Aachen, 52074, Germany
  • Charite Universitätsmeditin Berlin, Campus Virchow Klinikum
    Berlin, 13353, Germany
  • Universitätsklinikum Bonn
    Bonn, 53105, Germany
  • Klinikum Bremen Mitte
    Bremen, 28177, Germany
  • Klinikum Chemnitz gGmbH
    Chemnitz, 09113, Germany
  • GOKOS GmbH
    Dresden, 01307, Germany
  • Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
    Dresden, 01307, Germany
  • Universitätsklinikum Erlangen
    Erlangen, 91054, Germany
  • Universitätsklinikum Essen
    Essen, 45122, Germany
  • Universitätsklinikum Frankfurt
    Frankfurt, 60590, Germany
  • Universitätsklinikum Freiburg
    Freiburg im Breisgau, 79106, Germany
  • Universitätsklinikum Jena
    Jena, 07747, Germany
  • Universitätsklinikum Leipzig
    Leipzig, 04103, Germany
  • Gemeinschaftspraxis Dres. Müller/ Kröning/ Jentsch-Ullrich/ Tietze/ Krogel
    Magdeburg, 39104, Germany
  • Universitätsmedizin der Johannes- Gutenberg Universität Mainz
    Mainz, 55131, Germany
  • Universitätsmedizin Mannheim
    Mannheim, 68169, Germany
  • Universitätsklinikum Gießen und Marburg
    Marburg, 35043, Germany
  • Klinikum rechts der Isar
    München, 81675, Germany
  • Brüderkrankenhaus St. Josef Paderborn
    Paderborn, 33098, Germany
  • Krankenhaus Barmherzige Brüder Regensburg
    Regensburg, 93049, Germany
  • Universitätsklinikum Ulm
    Ulm, 89081, Germany
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03906292
Lead sponsor
University of Jena
Collaborators
Ludwig-Maximilians - University of Munich, Novartis Pharmaceuticals
Responsible party
Thomas Ernst, PD Dr. med. (Principal Investigator, University of Jena) — Principal investigator
First posted
Apr 8, 2019
Start date
Aug 19, 2019
Primary completion
Mar 2027 (estimated)
Completion
Dec 2027 (estimated)
Last update
Aug 18, 2026

Study contacts

Thomas Ernst, Prof. Dr.
principal investigator · University Hospital Jena

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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