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 Description

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

Condition or disease	Intervention/treatment	Phase
Chronic Myelogenous Leukemia (CML); Metastatic Gastrointestinal Stromal Tumors (GIST); Acute Lymphoblastic Leukemia (ALL); Receptor Tyrosine Kinase (KIT) Mutated Melanoma	Drug: Nilotinib	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 29, 2013
• Actual Primary Completion Date: July 7, 2023
• Actual Study Completion Date: July 7, 2023

Arms and Interventions

Arm

Intervention/treatment

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.

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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, New York

Novartis Investigative Site

Albany, New York, United States, 12208

United States, Texas

Novartis Investigative Site

Houston, Texas, United States, 77030

Austria

Novartis Investigative Site

Vienna, Austria, A 1090

Canada, British Columbia

Novartis Investigative Site

Vancouver, British Columbia, Canada, V5Z 4E6

Canada, Nova Scotia

Novartis Investigative Site

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Novartis Investigative Site

Hamilton, Ontario, Canada, L8V 5C2

Novartis Investigative Site

Toronto, Ontario, Canada, M5G1X5

France

Novartis Investigative Site

Lille, France, 59000

Novartis Investigative Site

Paris, France, 75571

Hong Kong

Novartis Investigative Site

Hong Kong SAR, Hong Kong

Hungary

Novartis Investigative Site

Budapest, Hungary, 1062

Novartis Investigative Site

Budapest, Hungary, 1097

Israel

Novartis Investigative Site

Haifa, Israel, 3109601

Italy

Novartis Investigative Site

Bologna, BO, Italy, 40138

Novartis Investigative Site

Genova, GE, Italy, 16147

Novartis Investigative Site

Modena, MO, Italy, 41124

Novartis Investigative Site

Roma, RM, Italy, 00161

Novartis Investigative Site

Candiolo, TO, Italy, 10060

Korea, Republic of

Novartis Investigative Site

Suwon, Gyeonggi-do, Korea, Republic of, 443380

Novartis Investigative Site

Seoul, Korea, Korea, Republic of, 05505

Novartis Investigative Site

Seoul, Korea, Republic of, 06351

Netherlands

Novartis Investigative Site

Amsterdam, Netherlands, 1081 HV

Novartis Investigative Site

Leiden, Netherlands, 2300 RC

Russian Federation

Novartis Investigative Site

Moscow, Russian Federation, 117198

Singapore

Novartis Investigative Site

Singapore, Singapore, 119228

Novartis Investigative Site

Singapore, Singapore, 169608

Slovakia

Novartis Investigative Site

Bratislava, Slovakia, 833 10

Spain

Novartis Investigative Site

Barcelona, Spain, 08041

Sweden

Novartis Investigative Site

Malmö, Sweden, SE-205 02

United Kingdom

Novartis Investigative Site

Cambridge, London, United Kingdom, CB2 2QQ

Novartis Investigative Site

London, United Kingdom, SW3 6JJ

Novartis Investigative Site

Manchester, United Kingdom, M20 4BX

Novartis Investigative Site

Newcastle upon Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] August 30, 2018

Statistical Analysis Plan  [PDF] July 21, 2023

More Information

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

Individual Participant Data (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/

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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

metastatic gastrointestinal stromal tumors (GIST); Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP),; adult; Chronic myelogenous leukemia (CML); chronic myeloid leukemia (CML); chronic myelocytic leukemia (CML); Acute Lymphoblastic Leukemia (ALL); Philadelphia chromosome positive; Acute Lymphoid Leukemia; suboptimal molecular response; Tasigna; CML; GIST; nilotinib

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Gastrointestinal Stromal Tumors; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Nilotinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action