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 )

Tracking Information

• First Submitted Date: November 14, 2012
• First Posted Date: November 28, 2012
• Results First Submitted Date: December 19, 2023
• Results First Posted Date: February 8, 2024
• Last Update Posted Date: February 8, 2024
• Actual Study Start Date: March 29, 2013
• Actual Primary Completion Date: July 7, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 6, 2024)

Number of Participants With Adverse Events and Serious Adverse Events [ 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. ]

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

Original Primary Outcome Measures (submitted: November 21, 2012)

Number of patients receiving [ Time Frame: Until no patients are left on study up to 10 years ]

To allow continued use of nilotinib to patients receiving nilotinib in a Novartis-sponsored Oncology CD&MA study which has reached its objectives and who are benefiting from treatment with nilotinib.

Current Secondary Outcome Measures (submitted: February 6, 2024)

Number of Participants With Clinical Benefit From Nilotinib [ 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. ]

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.

Original Secondary Outcome Measures (submitted: November 21, 2012)

• Frequency of serious adverse events [ Time Frame: Until no patients are left on study up to 10 years ]
  To collect long term data on serious adverse events.
• Nature of serious adverse events [ Time Frame: Until no patients are left on study up to 10 years ]
  To collect long term data on nature serious adverse events.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
• Official Title: 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
• Brief Summary: The purpose of this study was to allow continued use of nilotinib in patients who were on nilotinib treatment in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs (CD&MA) study and were benefiting from the treatment as judged by the investigator

Detailed Description

This was a multi-center, open label, single-arm, phase IV study to better characterize the long-term safety of nilotinib in patients treated in Novartis-sponsored studies and who benefited from treatment with nilotinib.

Patients who were enrolled in Novartis-sponsored nilotinib studies, had benefitted from treatment with nilotinib and fulfilled all requirements in the parent study could be enrolled into the current roll-over study.

There was no sample size estimation carried out for this study.

Patients returned to the study center on a quarterly basis (12 weeks ± 1 week) for scheduled visit. Adverse Events (AEs) (non-serious and serious AEs), clinical benefit assessment by investigator and study medication dispensing information were collected.

The original protocol of the current roll-over study was designed to provide continuation of treatment with nilotinib for patients enrolled in nilotinib studies. Therefore, the original protocol did not require AEs (non-serious and serious AEs) to be collected into the clinical database and only required serious adverse events (SAEs) to be collected in the Novartis safety database throughout the study duration.

The scheduled visit frequency was annually.

However, feedback from health authorities stated that all AEs should be collected. To account for this, the protocol was amended in 2016 (Protocol amendment 3 (PA 3)), with the primary objective changed to assess long-term safety of nilotinib. Consequently, PA 3 started to require all AEs (non-serious and serious AEs) to be entered into the clinical database, in addition to the continued SAE collection into the Novartis safety database. At the same time, the scheduled visit frequency was increased from annually to quarterly, and the protocol was also amended to require an investigator assessment of clinical benefit for patients.

• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Chronic Myelogenous Leukemia (CML)
• Metastatic Gastrointestinal Stromal Tumors (GIST)
• Acute Lymphoblastic Leukemia (ALL)
• Receptor Tyrosine Kinase (KIT) Mutated Melanoma

Intervention

Drug: Nilotinib

Patients who were on nilotinib treatment in a Novartis-sponsored study (parent study) and were benefiting from nilotinib treatment met the criteria for enrolment into the CAMN107A2409 study and to receive continued nilotinib treatment. The starting dose of nilotinib in the CAMN107A2409 study should have been the same as the last dose administered in the parent study. After the starting dose, the dose of nilotinib was based on the investigator's judgement. The dose of nilotinib should have been ≤ 800 mg/day for adult patients, 230mg/m2 body surface area (BSA) and ≤ 800 mg/day for pediatric patients.

Other Name: AMN107

Study Arms

Experimental: Nilotinib

Patients who were on nilotinib treatment in a Novartis-sponsored study (parent study) and were benefiting from nilotinib treatment met the criteria for enrolment into the CAMN107A2409 study and to receive continued nilotinib treatment. The starting dose of nilotinib in the CAMN107A2409 study should have been the same as the last dose administered in the parent study. After the starting dose, the dose of nilotinib was based on the investigator's judgement. The dose of nilotinib should have been ≤ 800 mg/day for adult patients, 230mg/m2 body surface area (BSA) and ≤ 800 mg/day for pediatric patients.

Intervention: Drug: Nilotinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 30, 2021): 57
• Original Estimated Enrollment (submitted: November 21, 2012): 300
• Actual Study Completion Date: July 7, 2023
• Actual Primary Completion Date: July 7, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

-Patient is currently enrolled in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs study receiving nilotinib and has fulfilled all their requirements in the parent study -Patient is currently benefiting from the treatment with nilotinib, as determined by the investigator -Patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements -Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures -Written informed consent obtained prior to enrolling in roll-over study

Exclusion Criteria:

- Patient has been permanently discontinued from nilotinib treatment in the parent study due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or any other reason - Patient has participated in a Novartis sponsored combination trial where nilotinib was dispensed in combination with another study medication and patient is still receiving combination therapy -Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval or inducing Torsade de Pointes and the treatment cannot be either safely discontinued at least one week prior to nilotinib treatment or switched to a different medication prior to start of nilotinib treatment and for the duration of the study -Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hcG laboratory test. -Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study and for 30 days after the final dose of nilotinib.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Canada, France, Hong Kong, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Russian Federation, Singapore, Slovakia, Spain, Sweden, United Kingdom, United States
• Removed Location Countries: Argentina, China, Germany, Thailand

Administrative Information

• NCT Number: NCT01735955
• Other Study ID Numbers: CAMN107A2409; 2012-003902-28 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

• URL: https://clinicalstudydatarequest.com/

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: February 2024