Chronic Myeloid LeukemiaPhase 2NAUTNCT02917720
2nd or 3rd TKI-stop After 2 Years Nilotinib Pre-treatment in CML-patients
A Phase 2 study testing TKI discontinuation and nilotinib in people with Chronic Myeloid Leukemia, run by European LeukemiaNet at 15 sites in 2 countries.
Trial summary
The main goal of the study is the assessment of duration of major molecular response (MMR) or better at 12 and 36 months after stopping tyrosine kinase inhibitors (TKI) therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within… 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?
- TKI discontinuation and nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 15 sitesin 2 countries
- Study dates
- Sep 2016to Sep 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
- Age ≥ 18 years
- Patients with Ph chromosome and/or the BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML
- CML in CP having failed a prior attempt to stop imatinib or other TKIs therapy either within EURO-SKI or not
- Pretreatment at least one year with any TKI after 1st stop
- Written informed consent
Who cannot join
- Previous hematological relapse after first stop of TKI.
- Failure to any TKI at any time during CML treatment according to current ELN criteria
- Previous planned or performed allo SCT
- Previous AP/BC at any time in the history of the disease
- High cardiac risk according to ESC score (≥ 10 Points)
- Impaired cardiac function including any of the following:
Show all 13Show fewer
- Use of a ventricular paced pacemaker; congenital long QT syndrome or family history of; history or presence of significant ventricular or atrial tachyarrhythmias; clinically significant resting bradycardia (<50 bpm); QTcF >450 msec at baseline, myocardial infarction before baseline; other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension).
- Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval is contraindicated.
- History of acute pancreatitis within one year of study entry or medical history of chronic pancreatitis.
- Positive hepatitis B virus serology test or HBV infection
- Any other malignancy except if neither clinically significant nor requires active intervention.
- Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, acute or chronic liver disease, pancreatic, or severe renal disease unrelated to tumor, active or uncontrolled infection).
- Women who are pregnant, breast feeding, or of childbearing potential without a negative serum pregnancy test at baseline. Male or female patients of childbearing potential unwilling to use an effective barrier contraceptive method
Trial locations and contacts
15 sites in 2 countries.
15 sites in 2 countries
Germany14 sites
Universitätsklinikum der RWTH
Aachen, 52074
Klinikum Bayreuth
Bayreuth, 95445
Klinikum Chemnitz
Chemnitz, 09113
Onkologische Schwerpunktpraxis
Esslingen am Neckar, 73728
Universitätsklinikum Freiburg
Freiburg im Breisgau, Baden-Wurttemberg, 79108
Universitätsklinikum Halle (Saale)
Halle
Medizinische Hochschule Hannover
Hannover, North Rhine-Westphalia, 30625
Schwerpunktpraxis Onkologie
Heilbronn, 74072
Universitätsmedizin Mannheim
Mannheim, Baden-Wurttemberg, 68167
Klinikum der Philipps-Universität
Marburg, 35033
Klinikum rechts der Isar
München, Bavaria, 81675
Kliniken Ostalb, Stauferklinikum Schwäbisch Gmünd
Mutlangen, 73557
Universitätsklinikum Rostock
Rostock, 18057
Schwarzwald-Baar Klinikum
Villingen-Schwenningen, 78052
About this study
Official title: Multicenter Prospective Trial After 1st or 2nd Unsuccessful Treatment Discontinuation in Chronic Myeloid Leukemia ( CML) Estimating the Efficacy of Nilotinib in Inducing the Persistence of Molecular Remission After Stopping TKI a 2nd or 3rd Time
The main goal of the study is the assessment of duration of major molecular response (MMR) or better at 12 and 36 months after stopping tyrosine kinase inhibitors (TKI) therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 (BCR-ABL ratio <0,01% on international Scale (IS) for at least one year and MR4.5 (BCR-ABL ratio <0,0032% on IS) for at least 6 months:
- who failed a first stop in the EURO-SKI study (standardized criteria)
- who failed a first or second stop outside the EURO-SKI study but would have had fulfilled same eligible criteria and were stopped according to EURO-SKI rules
- who failed a first or second stop outside the EURO-SKI study without fulfilling EURO-SKI rules
Read the detailed description
The proposal is to re-treat patients with a minimum of two years with nilotinib 2x300 mg/d resulting in total of at least three years TKI treatment who show recurrent disease after unsuccessful first or second stop after TKI treatment in or outside the EURO-SKI study.
If MR4 or better is re-achieved and maintained for at least one year and MR4.5 or better is re-achieved and maintained for at least 6 months, patients will be eligible for a second stop attempt within this study. For MR4, three consecutive PCRs with MR4 or deeper should be measured within one year and for MR4.5, two PCRs during 6 months should demonstrate a MR4.5.
Patients who exhibited hematological relapse after the first stop attempt will not be eligible for a second stop attempt within this study.
After inclusion, 3 monthly monitoring will be performed under nilotinib treatment within the trial. Patients fulfilling the criteria mentioned above will then enter the screening phase.
After verification of MR4.5, TKI treatment will be stopped and patients followed in the same manner as described in EURO-SKI (monthly PCRs for 6 months, 6-weekly PCRs 7-12 months after stopping, thereafter 3-monthly). If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted; here the same TKI (nilotinib) is recommended.
It is assumed that after failure of first (or second) stop a switch to treatment with 2GTKI may increase the chance of stopping a second (or third) time [Legros et al. Blood 2012; Rea et al. Blood 2014] It is expected that the rate of a successful second (or third) stop at 12 and 36 months is more than 25%.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- TKI discontinuation, nilotinib
- Keywords
- TKI discontinuation
- 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.
TKI discontinuationOther
2nd or 3rd TKI stop after pre-treatment with nilotinib.
nilotinibDrug
Pre-treatment with nilotinib 300 mg/bid for 2 years
| Study group | Role | What they receive |
|---|---|---|
| TKI-stop, pre-treatment with nilotinib | Experimental | Treatment after unsuccessful 1st or 2nd discontinuation at least two year with nilotinib (300 mg/bid). In total, retreatment with TKI for at least 3 years before entering screening for stopping phase is warranted. Clinical monitoring every 3 months during this 2 years.
Patients who re-achieved and maintained MR4 for at least 12 months and MR4.5 for at least 6 months can enter screening phase for TFR .If MR4.5 is confirmed by an validated laboratory, patient may enter stopping phase of the study. Patient not fulfilling these criteria can be screened again every 3 months until month 48. After TKI-stop hematological monitoring and quantitative PCR of BCR/ABL1 (month 1-6 after stopping: monthly; month 7-12 after stopping: every 1.5 months, thereafter once every three months, for 3 years in total.
Relapse is defined as BCR-ABL1 > 0.1% on IS at a single time point (loss of MMR) In case of relapse restart of TKI. In general, the same TKI (nilotinib) as before second stop is recommended Receives: Other: TKI discontinuation; Drug: nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second or third time
Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 for at least one year and MR4.5 for at least 6 months
Measured: 12 months after stopping
Secondary outcomes (9)
Assessment of quality of life (QoL) profiles under nilotinib treatment and comparison with previous TKI therapy before switch and after stopping
To investigate QoL changes over time in relapse-free patients without TKI re-start as measured by the EORTC QLQ-C30 and CML 24 (one combined questionnaire)
Measured: 5 years
Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI
Proportion of high risk patients according to the risk score at 6 months after stopping TKI;
Measured: 6 months after stopping
Estimation of overall survival
Overall survival is calculated from the date of 2nd stop of TKI treatment until the date of death irrespective of the cause of death. Patients still alive at the date of analysis will be censored at the date of last follow-up.
Measured: 3 years
Time to re-achievement of MR4.5 after restart of therapy
Assessment of molecular response after 3 years
Measured: 3 years
Number of patients with grade 1 through grade 5 adverse events (AEs) that are related to study drug, graded according to NCI CTCAE Version 3.0
Assessment of incidence of any AEs (e.g. from musculoskeletal system) that arise after stopping TKI treatment a second time
Measured: 3 years
Assessment of duration of MMR or better
Assessment of duration of MMR or better at 36 months after stopping TKI therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment
Measured: 36 months after stopping
Number of patients with grade 1 through grade 5 adverse events (AEs) that are related to study drug, graded according to NCI CTCAE Version 3.0
Assessment of incidence of any AEs (e.g. from musculoskeletal system) that arise after stopping TKI treatment a second time
Measured: 2 years treatment with nilotinib 300 mg/bid
Estimation of progression-free survival
Progression-free survival is defined as overall survival plus the additional events progression to accelerated phase or blast crisis that also terminate PFS
Measured: 3 years
Identification of clinical and biological factors correlating with the persistence of MMR or better after 6 months
Proportion of female patients without molecular relapse
Measured: 6 months after stopping
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2016 (estimated)
- Study startSep 2016
- Primary completionSep 2026 (estimated)
- Study completionSep 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- European LeukemiaNet
- Sponsor type
- Research network
- Collaborators
- Heidelberg University, Ludwig-Maximilians - University of Munich
- Responsible party
- Sponsor
- Investigators
- Susanne Geiselhart, Study chair, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02917720
- Sponsor's protocol ID
- ELN-002
- Other IDs
- 2015-004998-33, 2015
- Acronym
- NAUT
- Status last verified
- Sep 2025
- First submitted
- 2 Mar 2016
- Last updated
- 22 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Prospective Trial After 1st or 2nd Unsuccessful Treatment Discontinuation in Chronic Myeloid Leukemia ( CML) Estimating the Efficacy of Nilotinib in Inducing the Persistence of Molecular Remission After Stopping TKI a 2nd or 3rd Time
- ClinicalTrials.gov ID
- NCT02917720
- Acronym / sponsor ID
- NAUT / ELN-002
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- TKI discontinuation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 75 participants (actual)
- Lead sponsor
- European LeukemiaNetResearch network
- Collaborators
- Heidelberg University, Ludwig-Maximilians - University of Munich
- Study start
- Sep 2016 (actual)
- Primary completion
- Sep 2026 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 28 Sep 2016 (estimated)
- 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.
The main goal of the study is the assessment of duration of major molecular response (MMR) or better at 12 and 36 months after stopping tyrosine kinase inhibitors (TKI) therapy a second or third time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 (BCR-ABL ratio <0,01% on international Scale (IS) for at least one year and MR4.5 (BCR-ABL ratio <0,0032% on IS) for at least 6 months:
- who failed a first stop in the EURO-SKI study (standardized criteria)
- who failed a first or second stop outside the EURO-SKI study but would have had fulfilled same eligible criteria and were stopped according to EURO-SKI rules
- who failed a first or second stop outside the EURO-SKI study without fulfilling EURO-SKI rules
Detailed description
The proposal is to re-treat patients with a minimum of two years with nilotinib 2x300 mg/d resulting in total of at least three years TKI treatment who show recurrent disease after unsuccessful first or second stop after TKI treatment in or outside the EURO-SKI study.
If MR4 or better is re-achieved and maintained for at least one year and MR4.5 or better is re-achieved and maintained for at least 6 months, patients will be eligible for a second stop attempt within this study. For MR4, three consecutive PCRs with MR4 or deeper should be measured within one year and for MR4.5, two PCRs during 6 months should demonstrate a MR4.5.
Patients who exhibited hematological relapse after the first stop attempt will not be eligible for a second stop attempt within this study.
After inclusion, 3 monthly monitoring will be performed under nilotinib treatment within the trial. Patients fulfilling the criteria mentioned above will then enter the screening phase.
After verification of MR4.5, TKI treatment will be stopped and patients followed in the same manner as described in EURO-SKI (monthly PCRs for 6 months, 6-weekly PCRs 7-12 months after stopping, thereafter 3-monthly). If MMR is lost (BCR-ABL >0.1% (IS)), TKI treatment will once again be restarted; here the same TKI (nilotinib) is recommended.
It is assumed that after failure of first (or second) stop a switch to treatment with 2GTKI may increase the chance of stopping a second (or third) time [Legros et al. Blood 2012; Rea et al. Blood 2014] It is expected that the rate of a successful second (or third) stop at 12 and 36 months is more than 25%.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TKI-stop, pre-treatment with nilotinib | Experimental | Other: TKI discontinuation, Drug: nilotinibTreatment after unsuccessful 1st or 2nd discontinuation at least two year with nilotinib (300 mg/bid). In total, retreatment with TKI for at least 3 years before entering screening for stopping phase is warranted. Clinical monitoring every 3 months during this 2 years. Patients who re-achieved and maintained MR4 for at least 12 months and MR4.5 for at least 6 months can enter screening phase for TFR .If MR4.5 is confirmed by an validated laboratory, patient may enter stopping phase of the study. Patient not fulfilling these criteria can be screened again every 3 months until month 48. After TKI-stop hematological monitoring and quantitative PCR of BCR/ABL1 (month 1-6 after stopping: monthly; month 7-12 after stopping: every 1.5 months, thereafter once every three months, for 3 years in total. Relapse is defined as BCR-ABL1 > 0.1% on IS at a single time point (loss of MMR) In case of relapse restart of TKI. In general, the same TKI (nilotinib) as before second stop is recommended |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years
- Patients with Ph chromosome and/or the BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML
- CML in CP having failed a prior attempt to stop imatinib or other TKIs therapy either within EURO-SKI or not
- Pretreatment at least one year with any TKI after 1st stop
- Written informed consent
Key exclusion criteria (13 listed)
- Previous hematological relapse after first stop of TKI.
- Failure to any TKI at any time during CML treatment according to current ELN criteria
- Previous planned or performed allo SCT
- Previous AP/BC at any time in the history of the disease
- High cardiac risk according to ESC score (≥ 10 Points)
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 |
|---|---|---|
| TKI discontinuation2nd or 3rd TKI stop after pre-treatment with nilotinib. | Other | TKI-stop, pre-treatment with nilotinib |
| nilotinibPre-treatment with nilotinib 300 mg/bid for 2 years | Drug | TKI-stop, pre-treatment with nilotinib |
Primary outcome
Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second or third time
Time frame: 12 months after stopping
Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second time in patients with at least three years prior TKI treatment comprising at least two years of nilotinib treatment within this trial and maintained stable MR4 for at least one year and MR4.5 for at least 6 months
9 secondary outcomes
Assessment of quality of life (QoL) profiles under nilotinib treatment and comparison with previous TKI therapy before switch and after stopping
Time frame: 5 years
Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI
Time frame: 6 months after stopping
Estimation of overall survival
Time frame: 3 years
Time to re-achievement of MR4.5 after restart of therapy
Time frame: 3 years
Number of patients with grade 1 through grade 5 adverse events (AEs) that are related to study drug, graded according to NCI CTCAE Version 3.0
Time frame: 3 years
Assessment of duration of MMR or better
Time frame: 36 months after stopping
Number of patients with grade 1 through grade 5 adverse events (AEs) that are related to study drug, graded according to NCI CTCAE Version 3.0
Time frame: 2 years treatment with nilotinib 300 mg/bid
Estimation of progression-free survival
Time frame: 3 years
Identification of clinical and biological factors correlating with the persistence of MMR or better after 6 months
Time frame: 6 months after stopping
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 22 Sep 2025.
- Individual participant dataSharing planned: No
Related trials for Chronic Myeloid Leukemia
RecruitingObservational study
Collecting Blood Samples From Patients With and Without Cancer to Evaluate Tests for Early Cancer Detection
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia
Enrolling by invitationPhase 1
A Rollover Study for Continued Study Treatment and Ongoing Safety Monitoring
Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Chronic, B-Cell
RecruitingPhase 1
Phase 1 Study of 6MW5311 in Adults With Relapsed or Refractory Blood Cancers
AML, Multiple Myeloma
Not yet recruitingPhase 1/2
Phase 1/2 FLAG-IDA, VEN and Asciminib in CML and Ph+ AML
Myeloid Leukemia
RecruitingPhase 1
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Malignancy, Hematologic, Neoplasms, Hematologic
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.
Susanne Geiselhart study chair
Heidelberg University
15 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TKI discontinuation and nilotinib in people with Chronic Myeloid Leukemia, run by European LeukemiaNet at 15 sites in 2 countries.
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 5 inclusion and 13 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 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, Netherlands. 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?
Assessment of duration of MMR or better at 12 months after stopping TKI therapy a second or third time (time frame: 12 months after stopping). 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 22 Sep 2025.