Safety and Efficacy of CML Patients Who Switch to Nilotinib and Stop Treatment After Achieving and Sustaining MR4.5. (ENESTgoal)

This study is currently recruiting participants.
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01744665
First received: December 5, 2012
Last updated: February 26, 2014
Last verified: February 2014
  Purpose

To evaluate molecular relapse free rates 6 months after stopping nilotinib therapy in patients who achieve MR4.5


Condition Intervention Phase
CML
Drug: AMN107
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Multicenter Study of Treatment-free Remission in Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Patients Who Achieve and Sustain MR4.5 After Switching to Nilotinib

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentage of patients without molecular relapse after stopping nilotinib [ Time Frame: 6 months after stopping nilotinib therapy ] [ Designated as safety issue: No ]
    Proportion of patients without confirmed loss of MR4 within 6 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4, in the first 6 months after starting nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.


Secondary Outcome Measures:
  • Percentage of patients without molecular relapse after stopping nilotinib [ Time Frame: 12, 18, and 36 months after stopping nilotinib ] [ Designated as safety issue: No ]
    The proportion of patients without confirmed loss of MR4 at 12, 18, and 36 months following nilotinib TFR is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12, 18, and 36 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.

  • Proportion of patients who regain MR4.5 after restarting nilotinib due to molecular relapse [ Time Frame: 7 years ] [ Designated as safety issue: No ]
    The proportion of patients who regain MR4.5 after restarting nilotinib will be calculated as the number of patients who achieve MR4.5 after having lost MR4 divided by the number of patients who lost MR4.

  • Progression to AP/BC and death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC or death from any cause. [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    The estimation of progression-free survival (PFS) following nilotinib cessation will use the Kaplan-Meier (KM) method. PFS is measured from the date of cessation of nilotinib therapy to the date of the earliest of this event: progression to AP/BC or death from any cause. Patients not known to have progressed or died on or before the cut-off date for the KM analysis will have their PFS interval right-censored at the earlier of the date of their last assessment of molecular response status and the cut off date.

  • Overall survival (OS) defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause. [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    Kaplan-Meier (KM) estimation of OS. OS is measured from the date of start of nilotinib TFR phase to the date of death from any cause. If a patient is not known to have died, survival will be censored at the date of last contact.

  • Relapse free survival is defined as time from the date of nilotinib treatment discontinuation to the first documented molecular relapse (confirmed loss of MR4.0). [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
    Kaplan- Meier (KM) estimation method in each arm. Patients who drop out without relapse will be treated as censored observations.

  • Change in symptom-burden scores by the MDASI-CML assessment [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]
    The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) is a patient reported outcomes tool which will be used to assess the nature and impact of symptom burden on life on patients. The MDASI-CML consists of 19 validated symptom items and 6 validated core interference items. Each item is assessed on an 11 point scale, 0=Not Present and 10="As Bad as You can Imagine". The symptom, interference subscale total scores and the overall total score in MDASI-CML with their change from baseline will be summarized descriptively.

  • Change in healthy utility assessed by EQ-5D-3L [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]
    The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and the EQ visual analog scale. Each item has 3 levels (no problems, some problems and extreme problems) and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized overall and by treatments arms as appropriate at baseline and all post-baseline time points. Mean and standard deviation of the visual analog scale be provided.

  • Change in patient quality of life assessed by SF-8 [ Time Frame: From baseline to time to when MR4.5 is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase ] [ Designated as safety issue: No ]
    The SF-8 questionnaire consisting of 8 items (general health, physical functioning, rolephysical, bodily pain, vitality, social functioning, role-emotional and mental health) will be used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item has a 5 or 6 point response range. Physical and mental component summary measures (calculated using a norm-based scoring method given in the instrument guidelines) and each item score will be summarized at baseline and all post-baseline time points using mean and standard deviation.


Estimated Enrollment: 300
Study Start Date: May 2013
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AMN107 1 year of consolidation
300 patients will be enrolled to the study. Patients who achieve MR4.5 on study will then be randomized to receive a total of either 1 or 2 years of additional nilotinib therapy. If MR4.5 is sustained during the consolidation phase, patients will be eligible to stop taking niltoinib during the treatment-free remission (TFR) phase. No head to head comparison of the 2 arms will be performed. Each arm will be compared to historical data.
Drug: AMN107
Nilotinib will be provided by the sponsor as the study drug. Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.
Experimental: AMN107 2 years of consolidation
300 patients will be enrolled to the study. Patients who achieve MR4.5 on study will then be randomized to receive a total of either 1 or 2 years (Consolidation Phase) of additional nilotinib therapy. If MR4.5 is sustained during the Consolidation phase, patients will be eligible to stop taking niltoinib during the treatment-free remission (TFR) phase. No head to head comparison of the 2 arms will be performed. Each arm will be compared to historical data.
Drug: AMN107
Nilotinib will be provided by the sponsor as the study drug. Nilotinib will be provided as 150 mg capsules. Patients will take nilotinib 300mg twice daily on study and dose modifications to 450mg once daily is permitted per protocol.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of CML
  • Treated with at least 1 year of imatinib
  • Bcr-Abl level by PCR must be less than or equal to 0.1% and greater than 0.0032% by PCR reported on the International scale. This will be confirmed during screening
  • Written informed consent obtained prior to any screening procedures performed

Exclusion Criteria:

  • T315I mutation
  • Prior imatinib failure or had accelerated phase or blast crisis CML
  • Impaired cardiac function (defined futher in the protocol)
  • Pregnant or lactating women

Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01744665

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 72 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01744665     History of Changes
Other Study ID Numbers: CAMN107AUS37
Study First Received: December 5, 2012
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
CML, chronic myeloid leukemia, stop, niotinib, discontinue, imatinib, switch, MR4.5, undetectable, bcr-abl

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on April 17, 2014