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Efficacy and Safety of Nilotinib in CML-CP (ENESTKorea)

Primary Purpose

Chronic Myeloid Leukemia, Chronic Phase

Status

Completed

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

Nilotinib

About this trial

This is an interventional treatment trial for Chronic Myeloid Leukemia, Chronic Phase

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Aged 19 or older
Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase

Exclusion Criteria:

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
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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Investigational arm

Arm Description

Oral nilotinib 300mg twice daily with a 12-hour interval

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

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

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

Progression-free survival

Time from enrollment to documented disease progression or death from any cause

Overall survival

Time from enrollment to death from any cause

Full Information

NCT ID

NCT03332511

First Posted

October 30, 2017

Last Updated

November 1, 2017

Sponsor

Seoul National University Hospital

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03332511

Brief Title

Efficacy and Safety of Nilotinib in CML-CP

Acronym

ENESTKorea

Official Title

A Phase 4 Study of Nilotinib in Korean Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic Phase

Study Type

Interventional

2. Study Status

Record Verification Date

November 2017

Overall Recruitment Status

Completed

Study Start Date

May 6, 2013 (Actual)

Primary Completion Date

October 24, 2016 (Actual)

Study Completion Date

October 24, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Seoul National University Hospital

Collaborators

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Myeloid Leukemia, Chronic Phase

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

110 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Investigational arm

Arm Type

Experimental

Arm Description

Oral nilotinib 300mg twice daily with a 12-hour interval

Intervention Type

Drug

Intervention Name(s)

Nilotinib

Other Intervention Name(s)

Tasigna

Intervention Description

Nilotinib 300mg twice-daily

Primary Outcome Measure Information:

Title

Cumulative rate of molecular response 4.5 by 24 months

Description

Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.0032%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Cumulative rate of molecular response 3 by 24 months

Description

Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale

Time Frame

24 months

Title

Cumulative rate of molecular response 3 by 12 months

Description

Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.1%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale

Time Frame

12 months

Title

Cumulative rate of molecular response 4 by 24 months

Description

Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale

Time Frame

24 months

Title

Cumulative rate of molecular response 4 by 12 months

Description

Cumulative rate of BCR-ABL1 fusion transcripts ≤ 0.01%, measured by real-time quantitative polymerase chain reaction and standardized to the international scale

Time Frame

12 months

Title

Progression-free survival

Description

Time from enrollment to documented disease progression or death from any cause

Time Frame

24 months

Title

Overall survival

Description

Time from enrollment to death from any cause

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

19 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Aged 19 or older Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Inho Kim, MD

Organizational Affiliation

Seoul National University Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

Individual participant data are not currently planned to be shared.

Citations:

PubMed Identifier

29577674

Citation

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.

Results Reference

derived

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Efficacy and Safety of Nilotinib in CML-CP

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