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Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients

Extending Molecular Responses With Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) Patients in Chronic Phase

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01254188
Acronym
ENESTxtnd
Enrollment
421
Registered
2010-12-06
Start date
2011-04-30
Completion date
2014-11-30
Last updated
2016-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Myeloid Leukemia

Keywords

Chronic myeloid leukemia,, CML,, nilotinib,, myelogenous,, Philadelphia chromosome

Brief summary

This study will further investigate the safety and efficacy of nilotinib in newly diagnosed chronic myeloid leukemia patients in the chronic phase

Interventions

DRUGNilotinib

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.

Sponsors

Novartis Pharmaceuticals
Lead SponsorINDUSTRY

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

-Patients with chronic myeloid leukemia in the chronic phase diagnosed within 6 months of study entry

Exclusion criteria

* 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/

Design outcomes

Primary

MeasureTime frameDescription
The Percentage of Patients Achieving MMR by 12 Months12 monthsMMR 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

Secondary

MeasureTime frameDescription
Overall Survival3, 6, 9, 12, 15, 18, 21, 24 MonthsOS 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.
Duration of Major Molecular Response3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detectedKaplan-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
Complete Cytogenetic Response6 monthsComplete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.
Time to Molecular Response at 24 Months24 monthsEstimated median time to first MMR by Kaplan-Meier method
Kaplan-Meier Estimates of Progression-free Survival3,6,9,12,15,18,21,and 24 monthsPFS 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.
Kaplan-Meier Estimates of Failure-free Survival3,6,9,12,15,18,21,and 24 monthsTime 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.
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.6,12,18 and 24 months\* 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

Countries

Algeria, Argentina, Australia, Brazil, Canada, Egypt, India, Israel, Lebanon, Malaysia, Mexico, Oman, Russia, Saudi Arabia, South Africa, Taiwan, Thailand, Tunisia, United Arab Emirates

Participant flow

Participants by arm

ArmCount
Nilotinib
Nilotinib 300 mg BID
421
Total421

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyAdverse Event43
Overall StudyDeath4
Overall StudyDisease Progression6
Overall StudyLost to Follow-up5
Overall Studyper investigator discretion20
Overall StudyPregnancy2
Overall StudyProtocol Violation6
Overall StudyWithdrawal by Subject7

Baseline characteristics

CharacteristicNilotinib
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
53 Participants
Age, Categorical
Between 18 and 65 years
368 Participants
Age, Continuous47.13 years
STANDARD_DEVIATION 14.892
Sex: Female, Male
Female
195 Participants
Sex: Female, Male
Male
226 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
357 / 421
serious
Total, serious adverse events
97 / 421

Outcome results

Primary

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

Time frame: 12 months

ArmMeasureValue (NUMBER)
NilotinibThe Percentage of Patients Achieving MMR by 12 Months70.8 percentage of participants
Secondary

Complete Cytogenetic Response

Complete cytogenetic response (CCyR) is defined as a value of 0% Ph+ metaphases in bone marrow.

Time frame: 6 months

ArmMeasureValue (NUMBER)
NilotinibComplete Cytogenetic Response58.7 percentage of participants
Secondary

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

Time frame: 3, 6, 9, 12, 15, 18, 21, 24 Months after MMR was detected

Population: Full Analysis set, Number of events / censored 29/312.

ArmMeasureGroupValue (NUMBER)
NilotinibDuration of Major Molecular Response18 months90.8 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 3 Month Duration100 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 6 Month Duration97.1 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 9 Month Duration92.8 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 12 Month Duration92.1 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 15 Month Duration91.7 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 21 Month Duration89.7 percentage of participants
NilotinibDuration of Major Molecular ResponseK-M Estimate for 24 Month Duration85.2 percentage of participants
Secondary

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.

Time frame: 3,6,9,12,15,18,21,and 24 months

Population: FAS

ArmMeasureGroupValue (NUMBER)
NilotinibKaplan-Meier Estimates of Failure-free Survival24 mos88.8 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival3 mos97.4 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival6 mos95.9 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival9 mos94.6 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival12 mos93.6 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival15 mos92.0 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival18 mos91.0 percentage probability
NilotinibKaplan-Meier Estimates of Failure-free Survival21 mos89.7 percentage probability
Secondary

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.

Time frame: 3,6,9,12,15,18,21,and 24 months

Population: FAS

ArmMeasureGroupValue (NUMBER)
NilotinibKaplan-Meier Estimates of Progression-free Survival12 mos98.6 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival3 mos99.7 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival6 mos99.5 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival9 mos98.9 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival15 mos98.0 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival18 mos97.6 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival21 mos97.6 percentage probability
NilotinibKaplan-Meier Estimates of Progression-free Survival24 mos97.0 percentage probability
Secondary

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.

Time frame: 3, 6, 9, 12, 15, 18, 21, 24 Months

ArmMeasureGroupValue (NUMBER)
NilotinibOverall Survival3 months K-M Estimate99.8 percentage probability
NilotinibOverall Survival6 months K-M Estimate99.5 percentage probability
NilotinibOverall Survival9 months K-M Estimate99.5 percentage probability
NilotinibOverall Survival12 months K-M Estimate99.0 percentage probability
NilotinibOverall Survival15 months K-M Estimate98.2 percentage probability
NilotinibOverall Survival18 months K-M Estimate97.6 percentage probability
NilotinibOverall Survival21 months K-M Estimate97.6 percentage probability
NilotinibOverall Survival24 months K-M Estimate97.6 percentage probability
Secondary

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

Time frame: 6,12,18 and 24 months

ArmMeasureGroupValue (NUMBER)
NilotinibPercentage 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.6 mos after the first CCyR was achieved100 percentage of participants
NilotinibPercentage 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.12 mos after the first CCyR was achieved99.6 percentage of participants
NilotinibPercentage 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.18 mos after the first CCyR was achieved98.7 percentage of participants
NilotinibPercentage 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.24 mos after the first CCyR was achieved98.7 percentage of participants
Secondary

Time to Molecular Response at 24 Months

Estimated median time to first MMR by Kaplan-Meier method

Time frame: 24 months

Population: Full analysis set

ArmMeasureValue (MEDIAN)
NilotinibTime to Molecular Response at 24 Months6.0 Months

Source: ClinicalTrials.gov · Data processed: Mar 10, 2026