Chronic Myeloid LeukemiaPhase 3ENESTxtndNCT01254188
Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients
A Phase 3 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 100 sites in 19 countries.
Trial summary
This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase 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?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 421 participants
- Where
- 100 sitesin 19 countries
- Study dates
- Apr 2011to Nov 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry
Who cannot join
- Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide
- Uncontrolled congestive heart failure or hypertension
- Myocardial infarction or unstable angina pectoris within past 12 months
- Known T315I mutations
- QTcF >450 msec
- Significant arrhythmias
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
100 sites in 19 countries.
100 sites in 19 countries
Australia21 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Bedford Park, South Australia, 5042
Novartis Investigative Site
Box Hill, Victoria, 3128
Novartis Investigative Site
Canberra, Australian Capital Territory, 2605
Novartis Investigative Site
Clayton, Victoria, 3168
Novartis Investigative Site
Concord NSW, New South Wales, 2139
Novartis Investigative Site
Douglas, Queensland, 4810
Novartis Investigative Site
Fitzroy, Victoria, 3065
Novartis Investigative Site
Gosford, New South Wales, 2250
Novartis Investigative Site
Heidelberg, Victoria, 3084
Novartis Investigative Site
Hobart, Tasmania, 7000
Novartis Investigative Site
Kingswood, New South Wales, 2747
Novartis Investigative Site
Kogarah, New South Wales, 2217
Novartis Investigative Site
Liverpool, New South Wales, 2170
Novartis Investigative Site
Nedlands, Western Australia, 6009
Novartis Investigative Site
Parkville, Victoria, 3050
Novartis Investigative Site
Perth, Western Australia, 6000
Novartis Investigative Site
St Leonards, New South Wales, 2065
Novartis Investigative Site
Westmead, New South Wales, 2145
Novartis Investigative Site
Wodonga, Victoria, 3690
Novartis Investigative Site
Woolloongabba, Queensland, 4102
Canada18 sites
Novartis Investigative Site
Barrie, Ontario, L4M 6M2
Novartis Investigative Site
Brampton, Ontario, L6R 3J7
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Halifax, Nova Scotia, B3H 1V7
Novartis Investigative Site
Hamilton, Ontario, L8V 5C2
Novartis Investigative Site
London, Ontario, N6A 4G5
Novartis Investigative Site
Moncton, New Brunswick, E1C 6Z8
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Ottawa, Ontario, K1H 8L6
Novartis Investigative Site
Québec, Quebec, G1J 1Z4
Novartis Investigative Site
Saint John, New Brunswick, E2L 4L2
Novartis Investigative Site
Saskatoon, Saskatchewan, S7N 4H4
Novartis Investigative Site
St. John's, Newfoundland and Labrador, A1B 3V6
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1M9
Novartis Investigative Site
Vancouver, British Columbia, V6Z1Y6
Novartis Investigative Site
Weston, Ontario, M9N 1N8
Novartis Investigative Site
Windsor, Ontario, N8W 2X3
Russia16 sites
Novartis Investigative Site
Arkhangelsk, Russia, 163045
Novartis Investigative Site
Irkutsk, 664079
Novartis Investigative Site
Moscow, 125167
Novartis Investigative Site
Moscow, 125284
Novartis Investigative Site
Nizhny Novgorod, 603126
Novartis Investigative Site
Novosibirsk, Russia, 630051
Novartis Investigative Site
Perm, Russia, 614077
Novartis Investigative Site
Rostov-on-Don, 344022
Novartis Investigative Site
Rostov-on-Don, 344090
Novartis Investigative Site
Ryazan, Russia, 390039
Novartis Investigative Site
Saint Petersburg, Russia, 197341
Novartis Investigative Site
Saint Petersburg, 191024
Novartis Investigative Site
Saint Petersburg, 197022
Novartis Investigative Site
Tula, 300053
Novartis Investigative Site
Tyumen, Russia, 625023
Novartis Investigative Site
Yekaterinburg, 620137
Saudi Arabia5 sites
Novartis Investigative Site
Dammam, 15215
Novartis Investigative Site
Jeddah, 21423
Novartis Investigative Site
Jeddah, 21499
Novartis Investigative Site
Riyadh, 11211
Novartis Investigative Site
Riyadh, 11426
South Africa5 sites
Novartis Investigative Site
Bloemfontein, 9301
Novartis Investigative Site
Observatory, 7925
Novartis Investigative Site
Parktown, 2193
Novartis Investigative Site
Pretoria, 0002
Novartis Investigative Site
Soweto, Gauteng, 2013
Brazil4 sites
Novartis Investigative Site
Curitiba, Paraná, 81520-060
Novartis Investigative Site
Goiânia, Goiás, 74605-020
Novartis Investigative Site
Porto Alegre, Rio Grande do Sul, 90430-091
Novartis Investigative Site
Salvador, Estado de Bahia, 41253-190
Egypt4 sites
Novartis Investigative Site
Al Mansurah, 35516
Novartis Investigative Site
Alexandria, 21131
Novartis Investigative Site
Cairo, Cairo Governorate, 11566
Novartis Investigative Site
Cairo
Taiwan4 sites
Novartis Investigative Site
Linkou District, 33305
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
Novartis Investigative Site
Taichung, Taiwan, 40447
Novartis Investigative Site
Taipei, Taiwan, ROC, 112
Argentina3 sites
Novartis Investigative Site
Buenos Aires, Buenos Aires, C1114AAN
Novartis Investigative Site
Caba, Buenos Aires, C1221ADC
Novartis Investigative Site
Paraná, Entre Ríos Province, E3100BBJ
India3 sites
Novartis Investigative Site
Pune, Maharashtra, 411004
Novartis Investigative Site
Tamil Nadu, Chennai, 600035
Novartis Investigative Site
Vellore, Tamil Nadu, 632004
Israel3 sites
Novartis Investigative Site
Jerusalem, 9112001
Novartis Investigative Site
Petah Tikva, 49100
Novartis Investigative Site
Ramat Gan, 5266202
Algeria2 sites
Novartis Investigative Site
Algiers, Bouzareah, 16000
Novartis Investigative Site
Oran, 31000
Lebanon2 sites
Novartis Investigative Site
Beirut, 166830
Novartis Investigative Site
Saida, 652
Malaysia2 sites
Novartis Investigative Site
Kuala Selangor, 68000
Novartis Investigative Site
Pulau Pinang, 10990
Mexico2 sites
Novartis Investigative Site
Hermosillo, Sonora, 83000
Novartis Investigative Site
San Luis Potosí City, San Luis Potosí, 78416
Thailand2 sites
Novartis Investigative Site
Chiang Mai, 50200
Novartis Investigative Site
Muang, 40002
Tunisia2 sites
Novartis Investigative Site
Sousse, Tunisie, 4000
Novartis Investigative Site
Tunis, 1008
About this study
Official title: Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Nilotinib
- Keywords
- Chronic myeloid leukemia,, CML,, nilotinib,, myelogenous,, Philadelphia chromosome
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Philadelphia Chromosome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called AMN107
This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | 300 mg BID Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Percentage of Patients Achieving MMR by 12 Months
MMR is defined as BCR-ABL ratio (%) on IS <= 0.1% (corresponds to >=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method
Measured: 12 months
Secondary outcomes (7)
Time to Molecular Response at 24 Months
Estimated median time to first MMR by Kaplan-Meier method
Measured: 24 months
Duration of Major Molecular Response
Kaplan-Meier estimates of duration of first MMR among patients who achieved MMR (FAS) Duration of first MMR (months) = (Minimum date of (loss of first MMR , CML-related death, progression to AP/BC during study treatment, censoring) - date of first MMR + 1) / 30.4375
Measured: 3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected
Complete Cytogenetic Response
Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.
Measured: 6 months
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
- CCyR = 0% Ph+ metaphases based on at least 20 metaphases from bone marrow cytogenetics.
Duration of first CCyR (months) = (date of CCyR loss or censoring - date of first CCyR +1) / 30.4375
Measured: 6,12,18 and 24 months
Overall Survival
OS was defined as the time between date of study entry and date of death due to any cause at any time during the study, including the follow-up period after discontinuation of treatment.
Measured: 3, 6, 9, 12, 15, 18, 21, 24 Months
Kaplan-Meier Estimates of Progression-free Survival
PFS was defined as the time from the date of study entry to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause occurring on treatment.
Measured: 3,6,9,12,15,18,21,and 24 months
Kaplan-Meier Estimates of Failure-free Survival
Time to event (months) = (date of event or censoring - date of study entry + 1) / 30.4375. Date of event is the earliest date of the following events during treatment : discontinuation of nilotinib for nilotinib-related adverse events, death due to any cause, progression to AP or BC, loss of PCyR, loss of CCyR, loss of CHR. Time is censored at the date of last assessment in the trial for patients without event.
Measured: 3,6,9,12,15,18,21,and 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2010 (estimated)
- Study startApr 2011
- Primary completionNov 2014
- Study completionNov 2014
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 421 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
- NCT01254188
- Sponsor's protocol ID
- CAMN107E2401
- Acronym
- ENESTxtnd
- Status last verified
- Feb 2016
- First submitted
- 2 Dec 2010
- Last updated
- 3 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, Quach H, Pavlovsky C, Louw VJ, Shih LY, Turkina AG, Meillon L, Jin Y, Acharya S, Dalal D, Lipton JH. Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd. Br J Haematol. 2017 Oct;179(2):219-228. doi: 10.1111/bjh.14829. Epub 2017 Jul 12.
PubMed 28699641
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
- ClinicalTrials.gov ID
- NCT01254188
- Acronym / sponsor ID
- ENESTxtnd / CAMN107E2401
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- Chronic myeloid leukemia,, CML,, nilotinib,, myelogenous,, Philadelphia chromosome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 421 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Nov 2014 (actual)
- Study completion
- Nov 2014 (actual)
- First posted
- 6 Dec 2010 (estimated)
- Results
- Posted 3 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic 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: Nilotinib300 mg BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- -Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry
Key exclusion criteria (7 listed)
- Treatment with tyrosine kinase inhibitor or other antileukemic agents or treatments (including HSCT) for longer than 2 weeks, with exception of hydroxyurea and/or anagrelide
- Uncontrolled congestive heart failure or hypertension
- Myocardial infarction or unstable angina pectoris within past 12 months
- Known T315I mutations
- QTcF >450 msec
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: AMN107This was an open-label, single-arm, prospective, multi-center, Phase IIIb clinical study with nilotinib 300 mg bid treatment in newly diagnosed CML-CP patients not previously treated with imatinib therapy and diagnosed within 6 months of study entry. For patients insufficiently responding to nilotinib 300 mg bid, the dose may have been increased to 400 mg bid. Among patients with adverse events who had dose reduction, this study also allowed a possible re-escalation to 300 mg bid. | Drug | Nilotinib |
Primary outcome
The Percentage of Patients Achieving MMR by 12 Months
Time frame: 12 months
MMR is defined as BCR-ABL ratio (%) on IS <= 0.1% (corresponds to >=3 log reduction of BCR-ABL transcripts from standardized baseline value). Clopper-Pearson method
7 secondary outcomes
Time to Molecular Response at 24 Months
Time frame: 24 months
Duration of Major Molecular Response
Time frame: 3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected
Complete Cytogenetic Response
Time frame: 6 months
Percentage of Participants Estimated to Maintain Their First CCyR for 6, 12, 18, and 24 Months After the First CCyR Was Achieved as Determined by Kaplan Meier Estimatation.
Time frame: 6,12,18 and 24 months
Overall Survival
Time frame: 3, 6, 9, 12, 15, 18, 21, 24 Months
Kaplan-Meier Estimates of Progression-free Survival
Time frame: 3,6,9,12,15,18,21,and 24 months
Kaplan-Meier Estimates of Failure-free Survival
Time frame: 3,6,9,12,15,18,21,and 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28699641Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, Quach H, Pavlovsky C, Louw VJ, Shih LY, Turkina AG, Meillon L, Jin Y, Acharya S, Dalal D, Lipton JH. Nilotinib dose-optimization in newly diagnosed chronic myeloid leukaemia in chronic phase: final results from ENESTxtnd. Br J Haematol. 2017 Oct;179(2):219-228. doi: 10.1111/bjh.14829. Epub 2017 Jul 12.
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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
100 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Nilotinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 100 sites in 19 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 1 inclusion and 7 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 3 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 100 sites in Australia, Canada, Russia, Saudi Arabia, South Africa and 14 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 Mar 2016). 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?
The Percentage of Patients Achieving MMR by 12 Months (time frame: 12 months). 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 NCT01254188, 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 3 Mar 2016.