Chronic Myeloid Leukemia, Chronic PhasePhase 4ENESTKoreaNCT03332511
Efficacy and Safety of Nilotinib in CML-CP
A Phase 4 study testing Nilotinib in people with Chronic Myeloid Leukemia, Chronic Phase, run by Seoul National University Hospital.
Trial summary
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily) and its exposure-outcome relationship, in adult patients diagnosed as Philadelphia chromosome-positive chronic myeloid leukemia in chronic… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia, Chronic Phase
- 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
- 110 participants
- Where
- No sites listed yet
- Study dates
- 6 May 2013to 24 Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 19 or older
- Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase
Who cannot join
- CML with atypical BCR-ABL1 transcripts (transcripts other than e13a2 or e14a2)
- Eastern Cooperative Oncology Group performance status ≥ 3
- Cardiac abnormality including a corrected QT interval ≥ 480 milliseconds, complete left bundle branch block, permanent pacemaker implantation, congenital long QT syndrome, history of tachyarrhythmia requiring treatment, clinically significant resting bradycardia, history of acute coronary syndrome within 12 months, and decompensated congestive heart failure
- Organ dysfunction defined by total serum bilirubin levels ≥ 1.5 × the upper limit of the normal range (ULN), creatinine ≥ 1.5 × ULN, aspartate or alanine aminotransferase ≥ 2.5 × ULN, amylase or lipase ≥ 1.5 × ULN and alkaline phosphatase ≥ 2.5 × ULN not directly related to the CML
- Uncontrolled hypertension and/or diabetes
- Active and uncontrolled infection
Show all 13Show fewer
- Major surgery within two weeks or incomplete recovery from the previous surgery
- Congenital or acquired bleeding tendency
- Impaired gastrointestinal absorption
- History of small bowel resection or bypass surgery
- History of acute pancreatitis within 12 months or chronic pancreatitis
- Concomitant administration of strong irreplaceable CYP3A4 inhibitors or inducers, QT-prolonging agents, or coumarin derivatives
- Any other uncontrolled medical conditions that would present substantial safety risks or compromise compliance with the study treatment
About this study
Official title: A Phase 4 Study of Nilotinib in Korean Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic Phase
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily) and its exposure-outcome relationship, in adult patients diagnosed as Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
Read the detailed description
Nilotinib is a second-generation tyrosine kinase inhibitor with improved efficacy compared to imatinib. However, there are still many patients for whom the therapeutic response is inadequate, or toxicity is limiting the treatment. Serum concentration of nilotinib was shown to affect time to response and progression in previous studies. Therefore, the investigators hypothesized that the optimal plasma level of nilotinib that is sufficient to achieve adequate clinical response while not generating major adverse events could be elucidated by the analysis of combined clinical and pharmacokinetic data.
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily), in adult patients diagnosed as Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in chronic phase (CML-CP). Plasma samples are collected every three months, for up to 12 months, to determine plasma nilotinib concentrations (PNCs). The primary endpoint is the cumulative rate of molecular response 4.5 (MR4.5; BCR-ABL1IS ≤ 0.0032%) by 24 months. Secondary endpoints include the cumulative rates of MR3 (BCR-ABLIS ≤ 0.1%) and MR4 (BCR-ABLIS ≤ 0.01%) by 12 and 24 months; time to MR3, MR4, and MR4.5; progression-free survival (PFS); overall survival (OS). Correlations between PNCs and clinical outcomes are also analyzed.
- Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Being tested
- Nilotinib
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called Tasigna
Nilotinib 300mg twice-daily
| Study group | Role | What they receive |
|---|---|---|
| Investigational arm | Experimental | Oral nilotinib 300mg twice daily with a 12-hour interval Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative rate of molecular response 4.5 by 24 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.0032%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
Measured: 24 months
Secondary outcomes (6)
Cumulative rate of molecular response 3 by 24 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
Measured: 24 months
Cumulative rate of molecular response 3 by 12 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
Measured: 12 months
Cumulative rate of molecular response 4 by 24 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
Measured: 24 months
Cumulative rate of molecular response 4 by 12 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
Measured: 12 months
Progression-free survival
Time from enrollment to documented disease progression or death from any cause
Measured: 24 months
Overall survival
Time from enrollment to death from any cause
Measured: 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 Nov 2017
- Study start6 May 2013
- Primary completion24 Oct 2016
- Study completion24 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid Leukemia, Chronic PhaseStudies of the same condition, open and under way.
- More trials run by Seoul National University HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Principal investigator, Inho Kim, Seoul National University Hospital
- Investigators
- Inho Kim, MD, Principal investigator, Seoul National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03332511
- Sponsor's protocol ID
- 1110-124-383
- Acronym
- ENESTKorea
- Status last verified
- Nov 2017
- First submitted
- 30 Oct 2017
- Last updated
- 6 Nov 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data are not currently planned to be shared.
Publications
Shin J, Koh Y, Yoon SH, Cho JY, Kim DY, Lee KH, Kim HJ, Ahn JS, Kim YK, Park J, Sohn SK, Moon JH, Lee YJ, Yoon S, Lee JO, Cheong JW, Kim KH, Kim SH, Kim HG, Kim H, Nam SH, Do YR, Park SG, Park SK, Bae SH, Song HH, Shin DY, Oh D, Kim MK, Jung CW, Park S, Kim I. A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTKorea. Cancer Med. 2018 May;7(5):1814-1823. doi: 10.1002/cam4.1450. Epub 2018 Mar 25.
PubMed 29577674
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 4 Study of Nilotinib in Korean Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic Phase
- ClinicalTrials.gov ID
- NCT03332511
- Acronym / sponsor ID
- ENESTKorea / 1110-124-383
- Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Seoul National University HospitalUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 6 May 2013 (actual)
- Primary completion
- 24 Oct 2016 (actual)
- Study completion
- 24 Oct 2016 (actual)
- First posted
- 6 Nov 2017 (actual)
- 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.
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily) and its exposure-outcome relationship, in adult patients diagnosed as Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
Detailed description
Nilotinib is a second-generation tyrosine kinase inhibitor with improved efficacy compared to imatinib. However, there are still many patients for whom the therapeutic response is inadequate, or toxicity is limiting the treatment. Serum concentration of nilotinib was shown to affect time to response and progression in previous studies. Therefore, the investigators hypothesized that the optimal plasma level of nilotinib that is sufficient to achieve adequate clinical response while not generating major adverse events could be elucidated by the analysis of combined clinical and pharmacokinetic data.
ENESTKorea is a phase 4, multi-institutional, single-arm, open-label study investigating the efficacy and safety of nilotinib at the currently approved dose (300 mg twice daily), in adult patients diagnosed as Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in chronic phase (CML-CP). Plasma samples are collected every three months, for up to 12 months, to determine plasma nilotinib concentrations (PNCs). The primary endpoint is the cumulative rate of molecular response 4.5 (MR4.5; BCR-ABL1IS ≤ 0.0032%) by 24 months. Secondary endpoints include the cumulative rates of MR3 (BCR-ABLIS ≤ 0.1%) and MR4 (BCR-ABLIS ≤ 0.01%) by 12 and 24 months; time to MR3, MR4, and MR4.5; progression-free survival (PFS); overall survival (OS). Correlations between PNCs and clinical outcomes are also analyzed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Investigational arm | Experimental | Drug: NilotinibOral nilotinib 300mg twice daily with a 12-hour interval |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Aged 19 or older
- Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase
Key exclusion criteria (13 listed)
- CML with atypical BCR-ABL1 transcripts (transcripts other than e13a2 or e14a2)
- Eastern Cooperative Oncology Group performance status ≥ 3
- Cardiac abnormality including a corrected QT interval ≥ 480 milliseconds, complete left bundle branch block, permanent pacemaker implantation, congenital long QT syndrome, history of tachyarrhythmia requiring treatment, clinically significant resting bradycardia, history of acute coronary syndrome within 12 months, and decompensated congestive heart failure
- Organ dysfunction defined by total serum bilirubin levels ≥ 1.5 × the upper limit of the normal range (ULN), creatinine ≥ 1.5 × ULN, aspartate or alanine aminotransferase ≥ 2.5 × ULN, amylase or lipase ≥ 1.5 × ULN and alkaline phosphatase ≥ 2.5 × ULN not directly related to the CML
- Uncontrolled hypertension and/or diabetes
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: TasignaNilotinib 300mg twice-daily | Drug | Investigational arm |
Primary outcome
Cumulative rate of molecular response 4.5 by 24 months
Time frame: 24 months
Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.0032%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale
6 secondary outcomes
Cumulative rate of molecular response 3 by 24 months
Time frame: 24 months
Cumulative rate of molecular response 3 by 12 months
Time frame: 12 months
Cumulative rate of molecular response 4 by 24 months
Time frame: 24 months
Cumulative rate of molecular response 4 by 12 months
Time frame: 12 months
Progression-free survival
Time frame: 24 months
Overall survival
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2017.
- Derived from this study: PubMed 29577674Shin J, Koh Y, Yoon SH, Cho JY, Kim DY, Lee KH, Kim HJ, Ahn JS, Kim YK, Park J, Sohn SK, Moon JH, Lee YJ, Yoon S, Lee JO, Cheong JW, Kim KH, Kim SH, Kim HG, Kim H, Nam SH, Do YR, Park SG, Park SK, Bae SH, Song HH, Shin DY, Oh D, Kim MK, Jung CW, Park S, Kim I. A phase 4 study of nilotinib in Korean patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase: ENESTKorea. Cancer Med. 2018 May;7(5):1814-1823. doi: 10.1002/cam4.1450. Epub 2018 Mar 25.
- Individual participant dataSharing planned: No. Individual participant data are not currently planned to be shared.
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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.
Inho Kim, MD principal investigator
Seoul National University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nilotinib in people with Chronic Myeloid Leukemia, Chronic Phase, run by Seoul National University Hospital.
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 2 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: finished, as of the sponsor's last update on 6 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cumulative rate of molecular response 4.5 by 24 months (time frame: 24 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 NCT03332511, 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 6 Nov 2017.