Clinical Trial Results:
An open label, multi-center nilotinib roll-over protocol for patients who have completed a previous Novartis sponsored nilotinib study and are judged by the investigator to benefit from continued nilotinib treatment
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Summary
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EudraCT number |
2012-003902-28 |
Trial protocol |
AT IT ES HU NL GB SK SE FR |
Global end of trial date |
07 Jul 2023
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Results information
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Results version number |
v2(current) |
This version publication date |
01 Feb 2024
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First version publication date |
04 Jan 2024
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Other versions |
v1 |
Version creation reason |
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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 |
CAMN107A2409
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01735955 | ||
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 |
Novartis Campus, 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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
07 Jul 2023
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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 |
07 Jul 2023
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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 |
Primary objective - To evaluate long-term safety data (Serious Adverse Events (SAEs) and Adverse Events (AEs))
Secondary objective - To evaluate clinical benefit as assessed by the investigator
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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 |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
29 Mar 2013
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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 |
Austria: 1
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Country: Number of subjects enrolled |
Canada: 7
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Country: Number of subjects enrolled |
Spain: 2
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
Hong Kong: 3
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Country: Number of subjects enrolled |
Hungary: 6
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Country: Number of subjects enrolled |
Israel: 1
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Country: Number of subjects enrolled |
Italy: 6
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Country: Number of subjects enrolled |
Korea, Republic of: 5
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Country: Number of subjects enrolled |
Netherlands: 2
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Country: Number of subjects enrolled |
Russian Federation: 2
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Country: Number of subjects enrolled |
Singapore: 11
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Country: Number of subjects enrolled |
Slovakia: 1
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Country: Number of subjects enrolled |
Sweden: 1
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Country: Number of subjects enrolled |
United States: 3
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Worldwide total number of subjects |
57
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EEA total number of subjects |
21
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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) |
4
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Adolescents (12-17 years) |
3
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Adults (18-64 years) |
30
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From 65 to 84 years |
19
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85 years and over |
1
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||
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Pre-assignment
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Screening details |
The study had no screening period. 57 patients were enrolled and treated with nilotinib in this study. Pts were rolled over from 5 parent studies with the following indications: Chronic myelogenous leukemia (CML), Metastatic gastrointestinal stromal tumors (GIST), Acute lymphoblastic leukemia (ALL) & Receptor tyrosine kinase (KIT) mutated melanoma. | ||||||||||||||||||||
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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 |
Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
nilotinib
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Investigational medicinal product code |
AMN107
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Other name |
Tasigna
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
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Baseline characteristics reporting groups
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Reporting group title |
Nilotinib
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Reporting group description |
Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Nilotinib
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Reporting group description |
Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day | ||
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End point title |
Number of participants with adverse events and serious adverse events [1] | ||||||||||||||||||
End point description |
An Adverse Event (AE) is any untoward medical occurrence (eg any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.
Serious adverse event (SAE) case data were collected in the Safety Database. Adverse event (AE) data (both non-serious and serious) were collected in the Clinical database.
Max. = Maximum
Yrs = Years
Approx. = Approximately
eCRF = electronic Case Report Form
Time = timeframe
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End point type |
Primary
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End point timeframe |
SAE case data were collected the entire study duration after first dose of study treatment up to a max. time of approx. 10 yrs. AEs (both non-serious and serious) were collected in the eCRF 3 yrs after study initiation up to a max. time of approx. 7 yrs.
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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: NA for a single arm study and NA for AE data. |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of participants with clinical benefit from nilotinib | ||||||||||||||||||||||||||||||||||
End point description |
Number of patients (pts) with clinical benefit as assessed by investigator.
Clinical benefit data were first collected 3 years after study initiation and up to a maximum timeframe of approx. 7 years & 3 months at a patient level (up to Week 528 total at the study level).
Pts who discontinued in the first 3 years after study initiation didn’t have any clinical benefit data collected. Pts who enrolled in the first 3 years after study initiation only had clinical benefit data collected starting at approx. the third year of the study until the end of the patient’s participation in the study. Pts who enrolled after the first 3 years after study initiation had all clinical benefit data collected until the end of the patient’s participation in the study.
Data for the earlier time points are provided only for later enrolled pts. Data for the later time points are provided only for the earlier enrolled pts.
The time point per patient was calculated from the date of first drug intake.
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End point type |
Secondary
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End point timeframe |
Clinical benefit data were first collected 3 years after study initiation and are reported at baseline, Weeks 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 528.
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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 |
SAE case data were collected the entire study duration after first dose of study treatment up to a max. time of approx. 10 yrs. AEs (both non-serious and serious) were collected in the eCRF 3 yrs after study initiation up to a max. time of approx. 7 yrs.
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Adverse event reporting additional description |
Serious adverse event (SAE) case data were collected in the Safety Database. Adverse event (AE) data (both non-serious and serious) were collected in the Clinical database.
Max. = Maximum
Yrs = Years
Approx. = Approximately
eCRF = electronic Case Report Form
Time = timeframe
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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 |
26.0
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Reporting groups
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Reporting group title |
Nilotinib
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Reporting group description |
Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Sep 2013 |
Added monthly pregnancy tests for female patients of childbearing potential to reflect the
requirement of highly effective contraception for patients on nilotinib treatment.
Clarified that dose modifications were based on guidelines provided in the parent protocol, as
well as investigator’s judgment.
Clarified that patients could have access to the same strengths as specified in the parent
protocol.
Clarified that patients who were pregnant, who withdrew consent or died were required to be
withdrawn from the study. |
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24 Jun 2014 |
Incorporated guidance for the management of serum cholesterol and blood glucose increases,
other cardiac risk factors, and ischemic vascular or ischemic cardiovascular events occurring
in patients treated with nilotinib.
Updated the exclusion criteria relating to male trial participant’s use highly effective
contraception to be aligned with the current Investigator Brochure. |
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07 Apr 2016 |
Included the collection of all AEs (including non-serious and serious AEs) and an investigator
attestation of continued clinical benefit into the clinical database. Increased visit frequency
from annually to quarterly.
Included hepatitis B virus testing as one of the study procedures to identify study patients who
might have been at risk of hepatitis B reactivation.
Included collection of relevant medical history/current medical condition.
Included the study evaluation completion eCRF page. |
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27 Jul 2016 |
Corrected an error in the language regarding pregnancy outcome collection. Pregnancy
outcomes from female partners of any males who took study treatment was not collected in
this study as nilotinib is not genotoxic and no effects on sperm count, motility, or on fertility
were noted in animal studies. |
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30 Aug 2018 |
Provided further clarity to the end of study definition and trial timelines |
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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. | |||
| None reported | |||
