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

Gastrointestinal stromal tumors (GIST) are mesenchymal neoplasms that are
thought to arise from the interstitial cells of Cajal or their mesenchymal stem
cell precursor.

The management of GIST has evolved very rapidly since its molecular
pathogenesis was identified. GISTs are poorly responsive to chemotherapy(<10%
response rates) and the role of radiotherapy in their management is limited.
Surgery is the first-line therapy for resectable, non-metastatic GIST. However,
the majority of patients eventually develop recurrence or metastatic disease
(50-90%).

Imatinib is the first-line therapy for metastatic GIST with a median
progression free survival (PFS) reported between 18 and 29 months and a median
overall survival of 57 months. For patients whose disease has progressed
during, or who are intolerant to imatinib therapy, sunitinib is the available
second line treatment.

Thus, current available therapies may not be optimal for patients with
metastatic and/or unresectable GIST, and there is the potential for new
frontline agents with an improved safety and clinical benefit.

Nilotinib is a highly effective competitive inhibitor of the protein tyrosine
kinase activity of Bcr-Abl. In addition, nilotinib inhibits the tyrosine kinase
activity of KIT and PDGFR&; which are associated with GISTs. Although nilotinib
and imatinib exhibit similar potencies against the KIT and PDGFR target
enzymes, they exhibit major differences in cell transport. These differences
can give rise to much higher intracellular levels of nilotinib, compared to
imatinib.

In preclinical research is was found that nilotinib is a more potent inhibitor
of BCR-ABL tyrosine kinase compared to imatinib (Gleevec). In a clinical phase
II study (CAMN107A2101) a group of 119 Glivec-resistente or intolerante CML
patients were included. The first results show that treatment with nilotinib in
this group results in high hematologic and cytogenetic responses (respectively
92% and 53%). Furthermore, recent data was published from a small explorative
study in which a group of 13 newly diagnosed CML patients in the MD Anderson
Cancer Center (USA) were treated upfront with 400 mg B.I.D. nilotinib. After 3
months 93% of the patients reached a complete cytogenetic remission and
nilotinib was having an acceptable tolerability profile (in a historic
controlgroup in first-line treatment with 400 mg and 800 mg Gleevec response
percentages were seen of 37% and 61% respectively after 3 months).

The purpose of this study is to allow continued use of nilotinib in patients
who are on nilotinib treatment in a Novartis-sponsored, Oncology Clinical
Development & Medical Affairs (CD&MA) study and are benefiting from the
treatment as judged by the investigator. Which parent studies are eligible to
participate in the roll-over study will be decided by Novartis, Investigator
initiated trials (IITs) will not be included. All objectives of the parent
study must have been reached, and the parent study must be in the process of
being completed and reported.

Patients will continue to receive nilotinib until one of the following occurs:
the patient is no longer benefiting from the treatment, unacceptable toxicity
develops, consent is withdrawn, there is non-compliance with the protocol, the
investigator feels it is no longer in the patient*s best interest to continue
therapy, or the patient*s death.

This is a multi-center, open label, phase IV study to provide continued supply
of nilotinib to patients being treated in current Novartis-sponsored, Oncology
CD&MA studies and who are benefiting from treatment with nilotinib.

There will be no screening period for this study. At the enrollment visit the
patient will be consented to the study and eligible patients will start their
treatment with nilotinib. At this time, a yearly supply of nilotinib will be
dispensed to the patient/or as per local practice.

Patients must return to the study center on a yearly basis (+/- 3 months) for
resupply of study medication at which time limited drug dispensing information
will be collected. The patient may return to the clinic at any given time as
per standard of care, however, only one study visit per year will be recorded.
As Tasigna is a marketed drug with a well known safety profile, only reported
serious adverse events will be collected continuously throughout the study in
the safety database. For the safe and effective use of Tasigna, medical
monitoring should be performed as clinically indicated at the physician*s
discretion.

Patients will continue to be treated until they are no longer benefiting from
nilotinib treatment, develop unacceptable toxicities, withdraw consent, are
non-compliant to the protocol, the investigator feels it is no longer in the
patient*s best interest to continue nilotinib therapy or the patient dies,
whichever comes first.

A patient will reach the end of study when nilotinib treatment is permanently
discontinued and the end of treatment visit has been performed.

The study is expected to remain open for 10 years or until such time that
enrolled patients no longer need treatment with nilotinib, whichever comes
earlier.

Continuation treatment with nilotinib

Every potential side effect of nilotinib