study to allow access to nilotinib for patients who are on nilotinib treatment in a novartis-sponsored study

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

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

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.

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.

Keywords: 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