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Completed

NCT Number: NCT01744665

A Study That Switched Patients From Imatinib to Nilotinib and Then Was Followed by Treatment Cessation

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

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Key information

Conditions

CML Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alabama Comprehensive Cancer Center University of Alabama (8), Birmingham, Alabama, United States

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About this study

Study protocol included criteria for study termination that was met when > 2 patients lost CCyR during TFR phase (> 1% BCR-ABL); This study was terminated early as > 2 cases of confirmed loss of complete cytogenetic response were reported despite BCR-ABL monitoring during the TFR Phase. All cases achieved MR4.5 after Nilotinib treatment re-initiation and maintained until end of study; trial did not mandate re-initiation within 4 weeks after loss of MMR_ that was a requirement in other Nilotinib TFR trials Initial sample size was 300 patients with CML-CP; Amendment #2 in June 2015 reduced sample size to 59 due to recruitment challenges; Study endpoint analysis and interpretations of data were challenging due to small sample size for early study closure..

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 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
  • Pregnant or lactating women

Treatment and study plan

Nilotinib

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.

Other names: AMN107

Primary outcomes

  1. Percentage of Participants Without Molecular Relapse Within 6 Months After Starting the TFR Phase

    Time frame: 6 months after stopping nilotinib therapy

    Percentage of particpants without confirmed loss of MMR 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. Molecular relapse is defined as having a confirmed BCR-ABL ratio above MMR (2 consecutive BCR-ABL levels >0.1% IS taken approximately 4 weeks apart).

Secondary outcomes

  1. Relapse Free Survival is Defined as Time From the Date of Nilotinib Treatment Discontinuation to the First Documented Molecular Relapse (Confirmed Loss of MR4.5).

    Time frame: 7 years

    Relapse-free survival after the start of the TFR phase was summarized using the product-limit (Kaplan-Meier) estimates. The median for the relapse free survival and its 95% confidence intervals were provided. This analysis was performed on the FAS. Patients who dropped out without relapse were treated as censored observations.

  2. Percentage of Participants Without Molecular Relapse Within 12 and 24 Months After Starting the Treatment -Free Remission (TFR) Phase

    Time frame: 12 and 24 months after starting the TFR

    The percentage of participants without confirmed loss of MRR at 12 and 24 months is calculated by dividing the number of patients with no documented confirmed loss of MR4 at 12 and 24 months after starting the nilotinib TFR phase by the number of patients who entered nilotinib TFR phase.

  3. Percentage of Participants Who Regained MR4.5 After Restarting Nilotinib Due to Molecular Relapse

    Time frame: Restart of nilotinib up to month 6, 12 and 24

    The percentage of participants who regained MR4.5 after restarting nilotinib will be calculated as the number of patients who achieved MR4.5 after having lost MR4 divided by the number of patients who lost MR4.

  4. Number of Participants Who Progressed to Accelerated Phase/Blastic Crisis (AP/BC) or Died From From Any Cause.

    Time frame: Baseline up to approximately 5 years

    Progression to AP/BC and death where the "failure" event is the earliest occurrence of the following event: progression to AP/BC date.

  5. Overall Survival (OS)

    Time frame: Baseline up to approximately 5 years

    OS was defined as the time from the date of cessation of nilotinib therapy to the date of death from any cause.

  6. Change in Symptom-burden Scores by the M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML) Assessment

    Time frame: From baseline to time to when MR4.5 is confirmed, up to 24 months, and from end of Consolidation Phase to 6 and 12 months into the TFR Phase

    The M.D. Anderson Symptom Inventory for CML patients (MDASI-CML) was used to assess the nature and impact of symptom burden on life. It consisted of 20 validated symptom items and 6 validated interference items. Each item was assessed on an 11 point scale with responses from 0-10, 0=not present and 10=as bad as you can imagine. Symptom score (SS) was calculated when a patient scored at least 8 items of the symptom items using the formula: (sum of scores for the items answered) / number of items answered. If a subject responded to < 8 symptom items, the score was considered missing. Interference score (IS) was calculated when a patient scored at least 4 items using the formula: (sum of scores for the items answered)/number of items answered. If a subject responded to < 4 interference items, the score was considered missing. The total symptom score was 0-200 and total interference score was 0-60. Mean change from baseline was summarized at all post-baseline time points

  7. Change in Health Utility Assessed by EuroQol Group-5D-3L (EQ-5D-3L) Visual Analogue - Safety Set

    Time frame: From baseline to time to when MR4.5, up to 24 months, is confirmed and from end of Consolidation Phase to 6 and 12 months into the TFR Phase

    The EQ-5D-3L questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression and visual analog has a scale 0 to 100 (0=worst imaginable health state, 100=best imaginable health state).

  8. Change in Observed Scores for Patient Quality of Life Assessed by SF-8 - Safety Set

    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

    The SF-8 questionnaire consisted of 8 items (general health, physical functioning, role physical, bodily pain, vitality, social functioning, role-emotional and mental health) and was used to assess the impact of nilotinib treatment discontinuation on the quality of life. Each item had a 1 to 5 or 1 to 6 point response range and the higher number in the raw scores indicated poorer quality of life. The physical and mental component summary measures were calculated using a norm-based scoring method given in the instrument guidelines. These norm-based scores were summarized at baseline and mean change from baseline for post-baseline time points. The norm-based scores (based on the US population) had a mean of 50 and standard deviation of 10. Higher norm-based summary scores indicated better health

  9. Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 3 in Consolidation Phase - Safety Set

    Time frame: At month 3 in Consolidation Phase

    The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point

  10. Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Consolidation Phase - Safety Set

    Time frame: Month 12 in Consolidation Phase

    The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point

  11. Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 24 in Consolidation Phase - Safety Set

    Time frame: Month 24 in Consolidation Phase

    The EuroQol Five Dimensional Three-level (EQ-5D-3L) questionnaire comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point

  12. Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 6 in Treatment Free Remission Phase - Safety Set

    Time frame: Month 6 in in Treatment Free Remission Phase

    The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point

  13. Percentage of Participants' Scores at Each Level Assessed by EQ-5D-3L for Month 12 in Treatment Free Remission Phase - Safety Set

    Time frame: Month 12 in in Treatment Free Remission Phase

    The EuroQol Five Dimensional Three-level questionnaire (EQ-5D-3L) comprises 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each item has 3 levels (no problems, some problems and extreme problems). The percentages of patients at each level of the five items of the EQ-5D-3L will be summarized at each time point

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Acronym: ENESTgoal

Important dates

Study start
2013
Primary completion
2018
Study completion
2018
First posted
Dec 7, 2012
Registry last updated
Mar 10, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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