Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study

• ClinicalTrials.gov Identifier: NCT01735955
• Recruitment Status: Completed
• First Posted: November 28, 2012
• Results First Posted: February 8, 2024
• Last Update Posted: February 8, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Chronic Myelogenous Leukemia (CML); Metastatic Gastrointestinal Stromal Tumors (GIST); Acute Lymphoblastic Leukemia (ALL); Receptor Tyrosine Kinase (KIT) Mutated Melanoma
• Intervention: Drug: Nilotinib
• Enrollment: 57

Participant Flow

Recruitment Details
Pre-assignment Details	The study had no screening period. In total, 57 patients were enrolled and treated with nilotinib on this study. Patients were rolled over from 5 parent studies with the following indications: Chronic myelogenous leukemia (CML), Metastatic gastrointestinal stromal tumors (GIST), Acute lymphoblastic leukemia (ALL), and Receptor tyrosine kinase (KIT) mutated melanoma.

Arm/Group Title	Nilotinib
Arm/Group Description	Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
Period Title: Overall Study
Started	57
Completed	20
Not Completed	37
Reason Not Completed
Administrative problems	1
Patient/guardian decision	1
Patient withdrew consent	2
Physician Decision	4
Disease progression	24
Adverse Event	5

Baseline Characteristics

Arm/Group Title		Nilotinib
Arm/Group Description		Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
Overall Number of Baseline Participants		57
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants
	<=18 years	7 12.3%
	Between 18 and 65 years	30 52.6%
	>=65 years	20 35.1%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	57 participants
		53.02 (19.278)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	57 participants
	Female	30 52.6%
	Male	27 47.4%
Race and Ethnicity Not Collected [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	0 participants
		[1] Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events and Serious Adverse Events
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
Time Frame	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.

Outcome Measure Data

Analysis Population Description

safety set

Arm/Group Title	Nilotinib
Arm/Group Description:	Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
Overall Number of Participants Analyzed	57
Measure Type: Count of Participants; Unit of Measure: Participants
Adverse Events - total	29 50.9%
Adverse Events - Treatment-related adverse events	15 26.3%
SAEs - total	17 29.8%
SAEs - Treatment-related SAEs	2 3.5%
AEs leading to discontinuation - total	3 5.3%
AEs leading to discontinuation - Treatment-related AEs leading to discontinuation	3 5.3%

2. Secondary Outcome

Title	Number of Participants With Clinical Benefit From Nilotinib
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 and 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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Safety set

Arm/Group Title	Nilotinib
Arm/Group Description:	Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
Overall Number of Participants Analyzed	33
Measure Type: Number; Unit of Measure: Participants
Patients with clinical benefit - Baseline	15
Patients with clinical benefit - Week 24	11
Patients with clinical benefit - Week 48	17
Patients with clinical benefit - Week 72	11
Patients with clinical benefit - Week 96	19
Patients with clinical benefit - Week144	23
Patients with clinical benefit - Week 192	26
Patients with clinical benefit - Week 240	20
Patients with clinical benefit - Week 288	9
Patients with clinical benefit - Week 336	9
Patients with clinical benefit - Week 384	7
Patients with clinical benefit - Week 432	6
Patients with clinical benefit - Week 480	6
Patients with clinical benefit - Week 528	4

Adverse Events

Time Frame	Serious adverse event (SAE) case data were collected in the Safety Database the entire study duration after first dose of study treatment, up to a maximum timeframe of approx. 10 years. Adverse Event (AE) data (both non-serious and serious AEs) were collected in the Clinical Database 3 years after study initiation up to a maximum timeframe of approx. 7 years.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Nilotinib
Arm/Group Description	Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day
All-Cause Mortality
	Nilotinib
	Affected / at Risk (%)
Total	0/57 (0.00%)
Serious Adverse Events
	Nilotinib
	Affected / at Risk (%)
Total	17/57 (29.82%)
Cardiac disorders
Myocardial infarction † 1	1/57 (1.75%)
Myocardial ischaemia † 1	1/57 (1.75%)
Tachycardia † 1	1/57 (1.75%)
Gastrointestinal disorders
Abdominal pain † 1	1/57 (1.75%)
Abdominal pain upper † 1	1/57 (1.75%)
Intestinal obstruction † 1	1/57 (1.75%)
Melaena † 1	1/57 (1.75%)
Pancreatitis acute † 1	1/57 (1.75%)
Hepatobiliary disorders
Cholelithiasis † 1	1/57 (1.75%)
Infections and infestations
COVID-19 † 1	1/57 (1.75%)
Dengue fever † 1	1/57 (1.75%)
Infection † 1	1/57 (1.75%)
Pneumonia † 1	1/57 (1.75%)
Pyelonephritis acute † 1	1/57 (1.75%)
Urinary tract infection † 1	1/57 (1.75%)
Metabolism and nutrition disorders
Dehydration † 1	1/57 (1.75%)
Hypoglycaemia † 1	1/57 (1.75%)
Musculoskeletal and connective tissue disorders
Muscular weakness † 1	1/57 (1.75%)
Spinal osteoarthritis † 1	1/57 (1.75%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal stromal tumour † 1	1/57 (1.75%)
Malignant neoplasm progression † 1	1/57 (1.75%)
Nervous system disorders
Cerebral ischaemia † 1	1/57 (1.75%)
Ischaemic stroke † 1	1/57 (1.75%)
Psychiatric disorders
Delirium † 1	1/57 (1.75%)
Renal and urinary disorders
Hydronephrosis † 1	1/57 (1.75%)
Surgical and medical procedures
Small intestinal resection † 1	1/57 (1.75%)
Vascular disorders
Deep vein thrombosis † 1	1/57 (1.75%)
Peripheral arterial occlusive disease † 1	1/57 (1.75%)
Peripheral artery occlusion † 1	1/57 (1.75%)
1 Term from vocabulary, MedDRA (26.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Nilotinib
	Affected / at Risk (%)
Total	20/57 (35.09%)
Gastrointestinal disorders
Abdominal pain upper † 1	3/57 (5.26%)
General disorders
Fatigue † 1	3/57 (5.26%)
Infections and infestations
COVID-19 † 1	4/57 (7.02%)
Nasopharyngitis † 1	3/57 (5.26%)
Musculoskeletal and connective tissue disorders
Myalgia † 1	4/57 (7.02%)
Pain in extremity † 1	3/57 (5.26%)
Nervous system disorders
Headache † 1	5/57 (8.77%)
Paraesthesia † 1	3/57 (5.26%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	3/57 (5.26%)
Skin and subcutaneous tissue disorders
Alopecia † 1	4/57 (7.02%)
Vascular disorders
Hypertension † 1	3/57 (5.26%)
1 Term from vocabulary, MedDRA (26.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: + 1 862 778 8300
• EMail: Novartis.email@Novartis.com

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01735955
• Other Study ID Numbers: CAMN107A2409; 2012-003902-28 ( EudraCT Number )
• First Submitted: November 14, 2012
• First Posted: November 28, 2012
• Results First Submitted: December 19, 2023
• Results First Posted: February 8, 2024
• Last Update Posted: February 8, 2024