Clinical Trial Results:
A Phase IV single-arm, multicenter, open-label study assessing deep molecular response in adult patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase after two years of treatment with nilotinib 300 mg BID
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Summary
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EudraCT number |
2015-000968-34 |
Trial protocol |
DE |
Global end of trial date |
25 Mar 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Apr 2022
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First version publication date |
06 Apr 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CAMN107ADE20
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02546674 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
25 Mar 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Mar 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this trial was to evaluate the proportion of participants who are in deep molecular response MR4.5 (IS) at 24 months of study treatment, measured in a standardized EUTOS MR4.5 laboratory.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
18 Feb 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 171
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Worldwide total number of subjects |
171
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EEA total number of subjects |
171
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
128
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From 65 to 84 years |
42
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85 years and over |
1
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Recruitment
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Recruitment details |
The study was conducted across 73 centers in 1 country (Germany). | ||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 179 participants were screened in this study of which 8 discontinued screening phase and 171 participants were enrolled in the study | ||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||||
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Arms
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Arm title
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Nilotinib | ||||||||||||||||||||||||||
Arm description |
Participants with newly diagnosed CML in chronic phase received nilotinib 300 mg BID | ||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||
Investigational medicinal product name |
Nilotinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
A daily dose of 300 mg was given to all participants as two 150 mg capsules BID. The prescription of study drug was not study dependent and followed medical needs of the participant only. The study treatment was administered for 24 months.
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Baseline characteristics reporting groups
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Reporting group title |
Nilotinib
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Reporting group description |
Participants with newly diagnosed CML in chronic phase received nilotinib 300 mg BID | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nilotinib
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Reporting group description |
Participants with newly diagnosed CML in chronic phase received nilotinib 300 mg BID | ||
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End point title |
Percentage of participants with deep molecular response MR4.5 at 24 months of study treatment [1] | ||||||||
End point description |
Percentage of participants who were in deep molecular response MR4.5 (IS) at 24 months measured in a standardized EUTOS (European Treatment and Outcome Study for CML) MR4.5 laboratory. MR4.5 was defined as either (i) detectable disease ≤ 0.0032% BCR-ABL (fusion gene from breakpoint cluster region and Abelson genes) (IS) or (ii) undetectable disease in cDNA with 32000–99999 ABL1 transcripts or 77000–239999 glucuronidase beta (GUSB) transcripts.
Responders: Participants with a MR4.5 at 24 months, or if the assessment at this time point was missing, with a MR4.5 at 21 months
Non-responders: Participants dropping out early or not providing sufficient data for any other reason. Participants who achieved MR4.5 before 24 months, but was no longer in MR4.5 at 24 months or progressed (or was no longer in MR4.5 at 21 months if evaluation at 24 months was missing).
Confidence intervals were calculated based on the Exact Clopper-Pearson method.
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End point type |
Primary
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End point timeframe |
Month 24 and Month 21 (if assessment at Month 24 was missing)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses were planned for this endpoint |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with MR4 at 24 months of study treatment. | ||||||||
End point description |
Percentage of participants with MR4 at 24 months of study treatment. MR4 (IS) is defined as either (i) detectable disease ≤0.01% BCR-ABL by IS or (ii) undetectable disease in cDNA with 10000 – 31999 ABL1 transcripts or 24000 – 76999 GUSB transcripts.
Confidence intervals were calculated based on the Exact Clopper-Pearson method.
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End point type |
Secondary
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End point timeframe |
Month 24
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with major molecular response (MMR) at 12 months of study treatment | ||||||||
End point description |
Percentage of participants with MMR at 12 months of study treatment. MMR is defined as ≤ 0.1% BCR-ABL by IS, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline.
Confidence intervals were calculated based on the Exact Clopper-Pearson method.
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End point type |
Secondary
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End point timeframe |
Month 12
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of participants with complete cytogenetic response (CCyR) at 6 months of study treatment | ||||||||
End point description |
Percentage of participants with CCyR at 6 months of study treatment. Cytogenetic response was assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow (a review of a minimum of 20 metaphases was required). CCyR was defined as a value of 0% Ph+ metaphases in bone marrow.
Confidence intervals were calculated based on the Exact Clopper-Pearson method.
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End point type |
Secondary
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End point timeframe |
Month 6
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival | ||||||||
End point description |
Progression-free survival is defined as the time from the date of start of study treatment to the date of the first documented disease progression to accelerated phase (AP)/ blast crisis (BC) or death from any cause, whichever is earlier.
AP is defined as:
≥ 15% blasts in the peripheral blood or one marrow aspirate, but <30% blasts in both the peripheral blood and bone marrow aspirate
≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow aspirate
≥ 20% basophils in the peripheral blood or bone marrow Thrombocytopenia (<100 x 109/Liter) that is unrelated to therapy
Evidence of clonal evolution
BC is defined as:
≥ 30% blasts in peripheral blood or bone marrow aspirate
Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy (i.e., chloroma)
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End point type |
Secondary
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End point timeframe |
From date of start of treatment to first documented disease progression to AP/ BC or death, assessed up to 24 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to progression to AP/BC | ||||||||
End point description |
Time to progression to AP/BC is defined as the time from the date of start of study treatment to the date of earliest transformation to AP/BC, or CML-related death.
AP is defined as:
≥ 15% blasts in the peripheral blood or one marrow aspirate, but <30% blasts in both the peripheral blood and bone marrow aspirate
≥ 30% blasts plus promyelocytes in peripheral blood or bone marrow aspirate
≥ 20% basophils in the peripheral blood or bone marrow Thrombocytopenia (<100 x 109/L) that is unrelated to therapy
Evidence of clonal evolution (with consensus of SC only)
BC is defined as:
≥ 30% blasts in peripheral blood or bone marrow aspirate
Appearance of extramedullary involvement other than hepatosplenomegaly proven by biopsy (i.e., chloroma)
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End point type |
Secondary
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End point timeframe |
From the date of start of study treatment to the date of earliest transformation to AP/BC or CML-related death, assessed up to 24 months
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): global health status (GHS)/quality of life (QoL) | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a GHS/QoL scale.
The GHS/QoL scale has 7 possible scores of responses (1=very poor to 7=excellent). Scores were averaged and transformed to 0 to 100. Higher scores indicate better quality of life.
A positive change from Baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Physical functioning | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale.
For the physical functioning scale, participants self-rated levels of difficulty in doing strenuous activities, taking a walk, how much they needed to stay in bed or a chair, or needed help with eating, dressing, bathing, using the toilet. The physical functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in physical functioning.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Role functioning | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale.
For the role functioning scale, participants self-rated how much they were limited in doing work or daily activities, or in pursuing hobbies or other leisure time activities during the past week. The role functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in role functioning.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Emotional functioning | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale.
For the emotional functioning scale, participants self-rated how much they felt tense, worried, irritable or depressed during the past week. The emotional functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in emotional functioning.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Cognitive functioning | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale.
For the cognitive functioning scale, participants self-rated the extent of difficulty in concentrating on things or remembering things during the past week. The cognitive functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in cognitive functioning.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Social functioning | ||||||||||||||||||
End point description |
The EORTC QLQ-C30 is a patient completed 30 item questionnaire that is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, six single items and a global health status/QoL scale.
For the social functioning scale, participants self-rated how much their physical condition or medical treatment interfered with their family life and social activities during the past week. The social functioning scale had 4 possible scores (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores were averaged and transformed to 0 to 100. Higher scores indicate better functioning. A positive change from baseline indicates improvement in social functioning.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Symptom burden | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores were averaged and transformed to 0 to 100. A higher score in symptom burden domain indicates a worse outcome. A negative change from baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Impact on worry/mood | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each scale, scores were averaged and transformed to 0 to 100. A higher score in impact on worry/mood domain indicates a worse outcome. A negative change from baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Impact on daily life | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores were averaged and transformed to 0 to 100. A higher score in impact on daily life domain indicates a worse outcome. A negative change from baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Satisfaction with care and information | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores were averaged and transformed to 0 to 100. A higher score in satisfaction with care and information domain indicates a higher level of satisfaction. A positive change from baseline indicates increasing satisfaction.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Body image problems | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores were averaged and transformed to 0 to 100. A higher score in body image problems domain indicates a worse outcome. A negative change from baseline indicates improvement.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chronic Myeloid Leukemia specific 24 (EORTC QLQ-CML 24): Satisfaction with social life | ||||||||||||||||||
End point description |
The EORTC QLQ-CML 24 is an internationally developed disease specific health-related quality of life questionnaire for CML patients. The questionnaire is composed of four multi-item scales and two single-item scales. The module consists of 24 items assessing symptoms burden (13 items), impact on worry/mood (4 items), impact on daily life (3 items), satisfaction with care and information (2 items) body image problems (1 item) and satisfaction with social life (1 item). The items were measured on four levels: 1=not at all, 2=a little, 3=quite a bit, 4=very much. For each domain, scores were averaged and transformed to 0 to 100. A higher score in satisfaction with social life domain indicates a higher level of satisfaction. A positive change from baseline indicates increasing satisfaction.
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End point type |
Secondary
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End point timeframe |
Baseline, month 3, month 6, month 12, month 18 and month 24
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events were collected from first dose of study treatment until end of study treatment plus 30 days post treatment, up to maximum duration of 25 months
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Adverse event reporting additional description |
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Nilotinib (AMN107)
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Reporting group description |
Nilotinib (AMN107) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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11 Apr 2016 |
The primary purpose of this amendment is to include hepatitis B virus testing as one of the study procedures, to identify study patients who may be at risk of hepatitis B reactivation. |
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06 Nov 2017 |
The main purpose was to add an Interim Analysis of the data to the planned procedures and to prolong the recruitment period. |
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15 Feb 2021 |
The main purpose was to correct minor issues in previous versions and clarify exploratory points prior to data base lock. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to EudraCT system limitations, which EMA is aware of, data using 9999 as data points in this record are not an accurate representation of the clinical trial results. | |||
