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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03332511
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : November 6, 2017
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Inho Kim, Seoul National University Hospital

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.

Condition or disease Intervention/treatment Phase
Chronic Myeloid Leukemia, Chronic Phase Drug: Nilotinib Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 4 Study of Nilotinib in Korean Patients With Philadelphia Chromosome-positive Chronic Myeloid Leukemia in Chronic Phase
Actual Study Start Date : May 6, 2013
Actual Primary Completion Date : October 24, 2016
Actual Study Completion Date : October 24, 2016


Arm Intervention/treatment
Experimental: Investigational arm
Oral nilotinib 300mg twice daily with a 12-hour interval
Drug: Nilotinib
Nilotinib 300mg twice-daily
Other Name: Tasigna




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Cumulative rate of molecular response 3 by 24 months [ Time Frame: 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

  2. Cumulative rate of molecular response 3 by 12 months [ Time Frame: 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

  3. Cumulative rate of molecular response 4 by 24 months [ Time Frame: 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

  4. Cumulative rate of molecular response 4 by 12 months [ Time Frame: 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

  5. Progression-free survival [ Time Frame: 24 months ]
    Time from enrollment to documented disease progression or death from any cause

  6. Overall survival [ Time Frame: 24 months ]
    Time from enrollment to death from any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03332511


Sponsors and Collaborators
Seoul National University Hospital
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Inho Kim, MD Seoul National University Hospital

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Inho Kim, Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03332511    
Other Study ID Numbers: 1110-124-383
First Posted: November 6, 2017    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data are not currently planned to be shared.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases