Efficacy and Safety of Nilotinib in CML-CP

Chronic Myeloid Leukemia, Chronic Phase Clinical Trial

— ENESTKorea  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03332511
• Other study ID #: 1110-124-383
• Status: Completed
• Phase: Phase 4
• First received: October 30, 2017
• Last updated: November 1, 2017
• Start date: May 6, 2013
• Est. completion date: October 24, 2016

Study information

• Verified date: November 2017
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 phase.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 110
• Est. completion date: October 24, 2016
• Est. primary completion date: October 24, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia, Chronic Phase
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

Drug:
• Nilotinib
Nilotinib 300mg twice-daily

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Novartis Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	24 months
Secondary	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	24 months
Secondary	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	12 months
Secondary	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	24 months
Secondary	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	12 months
Secondary	Progression-free survival	Time from enrollment to documented disease progression or death from any cause	24 months
Secondary	Overall survival	Time from enrollment to death from any cause	24 months