Phase II Study of the IGF-1 Inhibitor Pasireotide Lar in Combination With the m-TOR Inhibitor Everolimus in Patients With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria:

- Histologically documented multiple myeloma

- Multiple myeloma relapsing or refractory to at least 2 of the currently accepted
therapies for multiple myeloma

- Age > 18 years

- Minimum of 4 weeks since any major surgery, radiation or 5 half life since prior
systemic anticancer therapy

- ECOG performance status ≤ 2

- Anticipated life expectancy of 12 weeks or more

- Adequate bone marrow function

- Adequate liver function

- Calculated creatinine

- INR ≤ 1.5

- Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤
2.5 x ULN

- Women of childbearing potential must have a negative serum pregnancy test. Women must
not be lactating. Both men and women of childbearing potential must be advised of
the importance of using effective birth control during the course of the study.

Exclusion Criteria:

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period.

- Patients should not receive immunization with attenuated live vaccines during study
period or within 1 week of study entry.

- Patients with prior or concurrent malignancy

- Patients with uncontrolled diabetes mellitus

- Patients who have congestive heart failure, unstable angina, sustained ventricular
tachycardia, ventricular fibrillation, clinically significant bradycardia, advanced
heart block or history of acute myocardial infarction within the 6 months preceding
enrollment.

- Liver disease

- Patients who have any severe and/or uncontrolled medical condition or other
conditions that could affect their participation in the study.

- Female patients who are pregnant or breast feeding, adults of reproductive potential
who are not using effective birth control methods.

- Male patients whose sexual partner(s) are women of child bering potential and who are
not willing to use adequate contraception during the study and for 8 weeks after the
end of treatment.

- Patients with a known hypersensitivity to everolimus or other rapamycin or to its
excipients.

- Known hypersensitivity to somatostatin analogues or any component of the pasireotide
or octreotide LAR formulations

- History of noncompliance to medical regimens

- Patients unwilling to or unable to comply with the protocol

- Patients taking medication know to inhibit, induce or be a substrate to isoenzyme
CYP3A

- QTcF at screening > 450 msec, history of syncope or family history of idiopathic
sudden death, sustained or clinically significant cardiac arrhythmias, risk factors
for Torsades de points, concomitant disease that could prolong QT intervals, use of
concomitant medications know to prolong the QT interval.