Chronic Myeloid LeukemiaPhase 2ENESTopNCT01698905
Treatment-free Remission After Achieving Sustained MR4.5 on Nilotinib (ENESTop)
A Phase 2 study testing nilotinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 62 sites in 18 countries.
Trial summary
A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 163 participants
- Where
- 62 sitesin 18 countries
- Study dates
- 20 Dec 2012to 29 Jan 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients >= 18 years of age
- ECOG Performance Status of 0, 1, or 2
- Patient with diagnosis of BCR-ABL positive CML CP
- Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial diagnosis
- Patient has at least 2 years of nilotinib treatment prior to study entry.
- Patient has achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
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- Adequate end organ function as defined by:
- Direct bilirubin ≤ 1.5 x ULN except for i) patient with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range)
- SGOT(AST) and SGPT(ALT) < 3 x ULN (upper limit of normal)
- Serum lipase ≤ 2 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN
- Serum creatinine < 1.5 x ULN
- Patients must have the following electrolyte values ≥ LLN (lower limit of normal) limits or corrected to within normal limits with supplements prior to the first dose of study medication:
- Potassium
- Magnesium
- Total calcium (corrected for serum albumin)
- Patients must have normal marrow function as defined below:
- Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- Written informed consent obtained prior to any screening procedures
Who cannot join
- Prior AP, BC or allo-transplant
- Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
- Patients with known atypical transcript
- CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)
- Dose reductions due to neutropenia or thrombocytopenia in the past 6 months
- Patient ever attempted to permanently discontinue imatinib or nilotinib treatment
Show all 31Show fewer
- Known impaired cardiac function including any one of the following:
- Inability to determine the QT interval on ECG
- Complete left bundle branch block
- Long QT syndrome or a known family history of long QT syndrome
- History of or presence of clinically significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia
- QTcF > 480 msec
- History or clinical signs of myocardial infarction within 1 year prior to study entry
- History of unstable angina within 1 year prior to study entry
- Other clinically significant heart disease (e.g. uncontrolled congestive heart failure or uncontrolled hypertension)
- Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes (defined as HbA1c > 9%), uncontrolled infection)
- History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis
- Known presence of a significant congenital or acquired bleeding disorder unrelated to cancer
- History of other active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer, previous cervical carcinoma in situ treated curatively
- Patients who have not recovered from prior surgery
- Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1
- Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. See Appendix 14.1 for a list of these medications. This list may not be comprehensive.
- Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John's Wort, and Ginkgo.
- Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to study entry. (Please see www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm for a list of agents that prolong the QT interval.)
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum pregnancy test before initiation of study treatment and must also use highly effective methods of contraception while enrolled in the study. The use of highly effective contraception should continue for at least 14 days after the last dose of study treatment or until the last day of TFR/TFR-2, or for the duration of a monthly cycle of oral contraception, whichever is longer. Acceptable forms of highly effective contraception methods include:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. 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 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). 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. In case of use of oral contraception, women should be stable on the same pill for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks prior to enrolling. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If a study patient becomes pregnant or is suspected of being pregnant during the study or within 30 days as part of safety evaluations after the final dose of nilotinib, the Study Doctor needs to be informed immediately and any ongoing study treatment with nilotinib has to be stopped immediately.
Trial locations and contacts
62 sites in 18 countries.
62 sites in 18 countries
Spain8 sites
Novartis Investigative Site
Alicante, 03010
Novartis Investigative Site
Badalona, Barcelona, 08916
Novartis Investigative Site
Madrid, 28006
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28046
Novartis Investigative Site
San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320
Novartis Investigative Site
Santander, Cantabria, 39008
Novartis Investigative Site
Seville, 41013
Japan7 sites
Novartis Investigative Site
Akita, 0108543
Novartis Investigative Site
Aomori, 0308553
Novartis Investigative Site
Chiba, 2608677
Novartis Investigative Site
Fukuoka, 8128582
Novartis Investigative Site
Kurume, Fukuoka, 830-0011
Novartis Investigative Site
Nagoya, Aichi-ken, 4648681
Novartis Investigative Site
Narita, Chiba, 286-8523
Brazil6 sites
Novartis Investigative Site
Belo Horizonte, Minas Gerais, 30130-100
Novartis Investigative Site
Campinas, São Paulo, 13083-970
Novartis Investigative Site
Goiânia, Goiás, 74605-050
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90035-003
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20211-030
Novartis Investigative Site
Rio de Janiero, Rio de Janeiro, 20231-050
United States5 sites
St Agnes Hospital
Baltimore, Maryland, 21229
Indiana Blood and Marrow Institute
Beech Grove, Indiana, 46107
University of Texas Medical Branch
Galveston, Texas, 77555-0144
USC Kenneth Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Compass Oncology
Vancouver, Washington, 98683
France5 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Grenoble, 38043
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Strasbourg, 67085
Novartis Investigative Site
Vandœuvre-lès-Nancy, 54511
Germany5 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Heilbronn, 74072
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
Novartis Investigative Site
Potsdam, 14467
Novartis Investigative Site
Ulm, 89081
Canada4 sites
Novartis Investigative Site
Hamilton, Ontario, L8V 5C2
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Québec, Quebec, G1J 1Z4
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Greece3 sites
Novartis Investigative Site
Athens, 106 76
Novartis Investigative Site
Athens, 185 47
Novartis Investigative Site
Larissa, 411 10
Israel3 sites
Novartis Investigative Site
Haifa, 3109601
Novartis Investigative Site
Petah Tikva, 4941492
Novartis Investigative Site
Ramat Gan, 5265601
Poland3 sites
Novartis Investigative Site
Gdansk, 80-952
Novartis Investigative Site
Krakow, Lesser Poland Voivodeship, 30-727
Novartis Investigative Site
Warsaw, 00-791
Russia3 sites
Novartis Investigative Site
Moscow, 125167
Novartis Investigative Site
Saint Petersburg, 191024
Novartis Investigative Site
Saint Petersburg, 197341
Argentina2 sites
Novartis Investigative Site
Buenos Aires, C1114AAN
Novartis Investigative Site
CABA, Buenos Aires, C1221ADC
Australia2 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Box Hill, Victoria, 3128
United Kingdom2 sites
Novartis Investigative Site
Liverpool, L7 8XP
Novartis Investigative Site
Nottingham, NG5 1PB
About this study
Official title: A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib
A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.
Read the detailed description
The Primary objective was to evaluate the percentage of patients in TFR within 48 weeks following nilotinib cessation.
This study originally consisted of seven phases (five treatment phases and two treatment-free phases) from which two were the focus of this primary analysis report (consolidation, TFR and treatment re-initiation) The study consisted of 2 main phases: Consolidation and TFR
Nilotinib treatment consolidation phase (NTCS): Patients who satisfied all inclusion/exclusion criteria were enrolled in the consolidation phase and continued to receive nilotinib for 52 weeks at the dose which the patient was receiving prior to study entry. If a patient maintained MR4.5 throughout the consolidation phase, he/she was eligible to enter in the TFR phase. If a patient had confirmed loss of MR4.5 during the consolidation phase, he/she was not eligible to enter in the TFR phase and continued nilotinib treatment.
Nilotinib TFR phase: Patients who were eligible to enter in the TFR phase after completing the 52 week consolidation phase stopped taking nilotinib on the first day of the TFR phase. Duration of this phase was up to 520 weeks after the last patient enters in the TFR phase.
Nilotinib treatment re-initiation phase (NTRI): If a patient had a confirmed loss of MR4 (two consecutive BCR-ABL >0.01% IS) or loss of MMR (BCR-ABL >0.1% IS) in the TFR phase, the patient restarted nilotinib treatment. Patients will be on nilotinib treatment for up to 520 weeks after the last patient entered the nilotinib TFR phase, or until a patient experience unacceptable toxicity, disease progression and/or treatment discontinued at the discretion of the Investigator or if the patient withdrew consent. Nilotinib cessation was not attempted for a second time in the patient who reinitiated treatment or discontinued following the TFR phase.
Nilotinib treatment continuation phase (NTCT) and Nilotinib treatment prolonged continuation phase (NTCT-P): Patients who were not eligible to enter into the TFR phase after completing the 52-week NTCS phase entered the nilotinib treatment continuation (NTCT) phase and would continue treatment with nilotinib for another 52 weeks (a total of 104 weeks of treatment). Patients who were not able to maintain MR4.5 and had a confirmed loss of MR4.5 during the NTCT phase were not eligible to enter the TFR-2 phase. These patients entered into the nilotinib prolonged treatment continuation phase (NTCT-P) and continued nilotinib treatment until 520 weeks after the last patient entered the nilotinib TFR phase, or until the patients experience unacceptable toxicity, disease progression and/or treatment would be discontinued at the discretion of the Investigator or withdrawal of consent.
Nilotinib TFR-2 phase: Patients who maintained MR4.5 during the NTCT phase were eligible to cease nilotinib treatment and enter the TFR-2 phase. The duration of the nilotinib TFR-2 phase is up to 520 weeks after the last patient entered the TFR phase. Patients stopped taking nilotinib therapy on the day they entered the TFR-2 phase.
Nilotinib treatment re-initiation-2 (NTRI-2): If a patient had a loss of MMR or a confirmed loss of MR4 during the TFR-2 phase, he/she entered the nilotinib treatment re-initiation-2 (NTRI-2) phase and resumed nilotinib treatment at a dose of either 300 mg or 400 mg bid.
Safety follow-up was performed within 30 days after the last dose of study treatment or the last day in TFR/TFR-2.
Post-treatment follow-up visits were performed every 12 weeks up to 520 weeks after the last patient entered the nilotinib TFR phase.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- nilotinib
- Keywords
- AMN107, CML, Phase II, single arm, open label, nilotinib, treatment-free remission, MR4.5, confirmed loss of MR4, loss of MMR, Ph+ CML-CP
- 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.
nilotinibDrug
Also called AMN107
Nilotinib was dosed by weight or body surface area.
Nilotinib 300 mg BID or 400 mg BID was be administered orally at approximately 12 hour intervals, and must not have been taken with food. The capsules were to be swallowed whole with water.
No food should have been consumed for at least 2 hours before the dose was taken and no additional food should have been consumed for at least one hour after the dose was taken. Patients were also allowed to enter this study on the same dose they were taking prior to study entry. Patients who required permanent dose reduction from their original starting dose were to be allowed to enter this study on the same dose only if the patient maintained this dose for a minimum of 6 months prior to study entry.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | Patients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening Receives: Drug: nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants in TFR Within 48-weeks Following Nilotinib Cessation
TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation.
Measured: first 48 weeks following nilotinib cessation
Secondary outcomes (8)
Percentage of Participants in TFR Within 96, 144, 192, 264 Weeks, and Within the End of Years 6, 7, 8, 9 and 10 Following Nilotinib Cessation
TFR is defined as no confirmed loss of MR4 (molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation.
Measured: first 96, 144, 192, 264 weeks, and within the end of years 6, 7, 8, 9 and 10 following nilotinib cessation.
Progression Free Survival (PFS) After the Start of the TFR Phase
Progression free survival, defined as the time from the date of start of TFR to the date of event defined as the first occurrence of documented disease progression to Accelerated phase/Blast Crises (AP/BC) or the date of death from any cause.
Measured: nilotinib cessation up to approximately 580 weeks
Treatment Free Survival (TFS) After the Start of the TFR Phase
Treatment-free survival defined as the time from the date of start of TFR to the date of earliest occurrence of any of the following events: loss of MMR, confirmed loss of MR4, re-initiation of nilotinib treatment due to any cause, progression to acute phase (AP) or blast crisis (BC) or death due to any cause.
Measured: nilotinib cessation up to approximately 580 weeks
Overall Survival (OS) After the Start of the TFR Phase
Overall survival, defined as the time from start date of TFR (date of entering the TFR phase) to date of death due to any cause at any time during the study, including the follow-up period after discontinuation of study up to LPLV. If a patient is not known to have died, survival will be censored at the date of last contact.
Measured: nilotinib cessation up to approximately 580 weeks
BCR-ABL Ratio (%) Over Time in Nilotinib Treatment Re-initiation Phase (NTRI)
ABL= Abelson leukemia virus and BCR=Break point cluster region. The BCR-ABL ratio (%) represents the level of BCR-ABL fusion gene transcripts relative to a control gene (ABL) measured in peripheral blood samples using quantitative reverse transcription polymerase chain reaction (RT-PCR). Results are expressed as a percentage on the International Scale (IS), a standardized reporting method that allows comparison across laboratories. The BCR-ABL ratio is used to assess the molecular response to treatment, with lower values indicating a reduced disease burden.
Measured: re-start of nilotinib up to approximately 48 weeks
Percentage of Participants With Stable MMR in Nilotinib Re-initiation Phase
Percentage of participants who were in stable MMR (stable MMR=BCR-ABL ≤ 0.1% IS) at multiple timepoints after achievement of that response in the nilotinib re-initiation phase for those timepoints.
Measured: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks after re-initiating Nilotinib in the NTRI Phase
Proportion of Participants With Stable MR4.5 in Nilotinib Re-initiation Phase
Percentage of participants who were in stable MR4.5 (stable MR4.5=BCR-ABL ≤ 0.0032% IS) at multiple time points after achievement of that response in the nilotinib re-initiation phase for those timepoints.
Measured: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks
Percentage of Participants With Stable MR4 in Nilotinib Re-initiation Phase
Percentage of participants who were in stable MR4 (stable MR4=BCR-ABL ≤ 0.01% IS) at multiple timepoints after achievement of that response in the nilotinib re-initiation phase for those timepoints.
Measured: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2012 (estimated)
- Study start20 Dec 2012
- Primary completion26 Nov 2015
- Study completion29 Jan 2025
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- 163 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01698905
- Sponsor's protocol ID
- CAMN107A2408
- Other IDs
- 2012-003186-18
- Acronym
- ENESTop
- Status last verified
- Jul 2026
- First submitted
- 1 Oct 2012
- Last updated
- 12 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Mahon FX, Boquimpani C, Kim DW, Benyamini N, Clementino NCD, Shuvaev V, Ailawadhi S, Lipton JH, Turkina AG, De Paz R, Moiraghi B, Nicolini FE, Dengler J, Sacha T, Takahashi N, Fellague-Chebra R, Acharya S, Wong S, Jin Y, Hughes TP. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018 Apr 3;168(7):461-470. doi: 10.7326/M17-1094. Epub 2018 Feb 20.
PubMed 29459949
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm, Open Label Study of Treatment-free Remission in Chronic Myeloid Leukemia (CML) Chronic Phase (CP) Patients After Achieving Sustained MR4.5 on Nilotinib
- ClinicalTrials.gov ID
- NCT01698905
- Acronym / sponsor ID
- ENESTop / CAMN107A2408
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- AMN107, CML, Phase II, single arm, open label, nilotinib, treatment-free remission, MR4.5
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 20 Dec 2012 (actual)
- Primary completion
- 26 Nov 2015 (actual)
- Study completion
- 29 Jan 2025 (actual)
- First posted
- 3 Oct 2012 (estimated)
- Results
- Posted 13 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A clinical research study to find out if it is safe to stop the drug nilotinib (Tasigna) in chronic myeloid leukemia (CML) patients. Patients who started treatment with imatinib (Gleevec) when they were first diagnosed with CML, then switched to nilotinib (Tasigna) for at least 2 years with the combined time on imatinib (Gleevec) and nilotinib (Tasigna) for at least 3 years and have very small amount of leukemia cells remaining after the nilotinib (Tasigna) treatment will qualify for the study.
Detailed description
The Primary objective was to evaluate the percentage of patients in TFR within 48 weeks following nilotinib cessation.
This study originally consisted of seven phases (five treatment phases and two treatment-free phases) from which two were the focus of this primary analysis report (consolidation, TFR and treatment re-initiation) The study consisted of 2 main phases: Consolidation and TFR
Nilotinib treatment consolidation phase (NTCS): Patients who satisfied all inclusion/exclusion criteria were enrolled in the consolidation phase and continued to receive nilotinib for 52 weeks at the dose which the patient was receiving prior to study entry. If a patient maintained MR4.5 throughout the consolidation phase, he/she was eligible to enter in the TFR phase. If a patient had confirmed loss of MR4.5 during the consolidation phase, he/she was not eligible to enter in the TFR phase and continued nilotinib treatment.
Nilotinib TFR phase: Patients who were eligible to enter in the TFR phase after completing the 52 week consolidation phase stopped taking nilotinib on the first day of the TFR phase. Duration of this phase was up to 520 weeks after the last patient enters in the TFR phase.
Nilotinib treatment re-initiation phase (NTRI): If a patient had a confirmed loss of MR4 (two consecutive BCR-ABL >0.01% IS) or loss of MMR (BCR-ABL >0.1% IS) in the TFR phase, the patient restarted nilotinib treatment. Patients will be on nilotinib treatment for up to 520 weeks after the last patient entered the nilotinib TFR phase, or until a patient experience unacceptable toxicity, disease progression and/or treatment discontinued at the discretion of the Investigator or if the patient withdrew consent. Nilotinib cessation was not attempted for a second time in the patient who reinitiated treatment or discontinued following the TFR phase.
Nilotinib treatment continuation phase (NTCT) and Nilotinib treatment prolonged continuation phase (NTCT-P): Patients who were not eligible to enter into the TFR phase after completing the 52-week NTCS phase entered the nilotinib treatment continuation (NTCT) phase and would continue treatment with nilotinib for another 52 weeks (a total of 104 weeks of treatment). Patients who were not able to maintain MR4.5 and had a confirmed loss of MR4.5 during the NTCT phase were not eligible to enter the TFR-2 phase. These patients entered into the nilotinib prolonged treatment continuation phase (NTCT-P) and continued nilotinib treatment until 520 weeks after the last patient entered the nilotinib TFR phase, or until the patients experience unacceptable toxicity, disease progression and/or treatment would be discontinued at the discretion of the Investigator or withdrawal of consent.
Nilotinib TFR-2 phase: Patients who maintained MR4.5 during the NTCT phase were eligible to cease nilotinib treatment and enter the TFR-2 phase. The duration of the nilotinib TFR-2 phase is up to 520 weeks after the last patient entered the TFR phase. Patients stopped taking nilotinib therapy on the day they entered the TFR-2 phase.
Nilotinib treatment re-initiation-2 (NTRI-2): If a patient had a loss of MMR or a confirmed loss of MR4 during the TFR-2 phase, he/she entered the nilotinib treatment re-initiation-2 (NTRI-2) phase and resumed nilotinib treatment at a dose of either 300 mg or 400 mg bid.
Safety follow-up was performed within 30 days after the last dose of study treatment or the last day in TFR/TFR-2.
Post-treatment follow-up visits were performed every 12 weeks up to 520 weeks after the last patient entered the nilotinib TFR phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: nilotinibPatients with minimum 3 years of tyrosine kinase inhibitor treatment (first with imatinib and then switched to nilotinib) since initial diagnosis, at least 2 years of nilotinib treatment prior to study entry and who achieved MR4.5 (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Male or female patients >= 18 years of age
- ECOG Performance Status of 0, 1, or 2
- Patient with diagnosis of BCR-ABL positive CML CP
- Patient has received a minimum of 3 years of tyrosine kinase inhibitor treatment (first with imatinib (> 4 weeks) and then switched to nilotinib) since initial diagnosis
- Patient has at least 2 years of nilotinib treatment prior to study entry.
Key exclusion criteria (31 listed)
- Prior AP, BC or allo-transplant
- Patient has documented MR4.5 at the time when switched from imatinib to nilotinib
- Patients with known atypical transcript
- CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past)
- Dose reductions due to neutropenia or thrombocytopenia in the past 6 months
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 |
|---|---|---|
| nilotinibAlso: AMN107Nilotinib was dosed by weight or body surface area. Nilotinib 300 mg BID or 400 mg BID was be administered orally at approximately 12 hour intervals, and must not have been taken with food. The capsules were to be swallowed whole with water. No food should have been consumed for at least 2 hours before the dose was taken and no additional food should have been consumed for at least one hour after the dose was taken. Patients were also allowed to enter this study on the same dose they were taking prior to study entry. Patients who required permanent dose reduction from their original starting dose were to be allowed to enter this study on the same dose only if the patient maintained this dose for a minimum of 6 months prior to study entry. | Drug | Nilotinib |
Primary outcome
Percentage of Participants in TFR Within 48-weeks Following Nilotinib Cessation
Time frame: first 48 weeks following nilotinib cessation
TFR is defined as no confirmed loss of MR4 (Molecular response 4.0 log reduction from baseline) or loss of MMR (major molecular response) and no re-starting of nilotinib therapy within 12 months following cessation of nilotinib. Confirmed loss of MR4 is two consecutive BCR-ABL > 0.01% IS. Loss of MMR does not require confirmation.
8 secondary outcomes
Percentage of Participants in TFR Within 96, 144, 192, 264 Weeks, and Within the End of Years 6, 7, 8, 9 and 10 Following Nilotinib Cessation
Time frame: first 96, 144, 192, 264 weeks, and within the end of years 6, 7, 8, 9 and 10 following nilotinib cessation.
Progression Free Survival (PFS) After the Start of the TFR Phase
Time frame: nilotinib cessation up to approximately 580 weeks
Treatment Free Survival (TFS) After the Start of the TFR Phase
Time frame: nilotinib cessation up to approximately 580 weeks
Overall Survival (OS) After the Start of the TFR Phase
Time frame: nilotinib cessation up to approximately 580 weeks
BCR-ABL Ratio (%) Over Time in Nilotinib Treatment Re-initiation Phase (NTRI)
Time frame: re-start of nilotinib up to approximately 48 weeks
Percentage of Participants With Stable MMR in Nilotinib Re-initiation Phase
Time frame: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks after re-initiating Nilotinib in the NTRI Phase
Proportion of Participants With Stable MR4.5 in Nilotinib Re-initiation Phase
Time frame: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks
Percentage of Participants With Stable MR4 in Nilotinib Re-initiation Phase
Time frame: at 48 weeks, 96 weeks, 144 weeks, 192 weeks, 240 weeks, 288 weeks, 336 weeks, 384 weeks and 432 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29459949Mahon FX, Boquimpani C, Kim DW, Benyamini N, Clementino NCD, Shuvaev V, Ailawadhi S, Lipton JH, Turkina AG, De Paz R, Moiraghi B, Nicolini FE, Dengler J, Sacha T, Takahashi N, Fellague-Chebra R, Acharya S, Wong S, Jin Y, Hughes TP. Treatment-Free Remission After Second-Line Nilotinib Treatment in Patients With Chronic Myeloid Leukemia in Chronic Phase: Results From a Single-Group, Phase 2, Open-Label Study. Ann Intern Med. 2018 Apr 3;168(7):461-470. doi: 10.7326/M17-1094. Epub 2018 Feb 20.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
62 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing nilotinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 62 sites in 18 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 21 inclusion and 31 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: finished, as of the sponsor's last update on 12 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 62 sites in Spain, Japan, Brazil, United States, France and 13 more countries. 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 13 Jan 2021). 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?
Percentage of Participants in TFR Within 48-weeks Following Nilotinib Cessation (time frame: first 48 weeks following nilotinib cessation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01698905, which also lists 1 linked publication.
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 12 Aug 2026.