Safety and Efficacy of RAD001 in Patients With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® Therapy. (PILLAR-1)

Inclusion Criteria:

• Adult patients (> 18 years old) with Mantle Cell Lymphoma that has been confirmed by central pathology review (archival diagnostic tumor specimen required)
• Patients with mantle cell lymphoma who have documented refractory disease to bortezomib (Velcade®) or who have documented intolerance to Velcade® therapy. Intolerance to Velcade® is determined by the study investigator based on clinical evaluations. Patients are considered refractory to Velcade® if they have documented radiological progression on or within 12 months of last dose of Velcade® when given alone or, on or within 12 months from the last dose of the last component of a combination therapy which included Velcade®). Patients are considered refractory to Velcade®, if Velcade® is part of a combination treatment for the disease.
• Patients must have received at least one prior antineoplastic agent, other than Velcade® either separately or in combination with bortezomib (Velcade®).
• At least one site of measurable nodal disease at baseline >2.0 cm in the longest transverse diameter and clearly measurable in at least two perpendicular dimensions, as determined by CT scan (or MRI, only if CT scan can not be performed)
• ECOG performance status = 0, 1 or 2
• Life expectancy ≥ 3 months
• Adequate bone marrow, liver and renal function
• Platelets ≥ 75 x 109/L (untransfused platelets)

Exclusion Criteria:

• Patients who are currently receiving anticancer therapies or have received anticancer therapies within 4 weeks of the start of study drug (including chemotherapy, radiation, antibodies, targeted therapy etc.) are not eligible
• Previous treatment with mTOR inhibitors (e.g. everolimus, sirolimus, temsirolimus, etc)
• Patients with prior allogeneic stem cell transplant
• Grade 3 or 4 unresolved toxicity from prior antineoplastic therapies
• Currently taking other investigational agents or received other investigational drugs within 4 weeks of the start of study drug
• Patients with CNS lymphoma are not eligible; head MRI (or CT if MRI is not available) is required prior to study entry
• Use of chronic, systemic corticosteroids or another immunosuppressive agent, except prednisone ≤ 20 mg daily (or equivalent) for adrenal insufficiency (must have been on a stable dosage regimen for ≥ 4 weeks prior to the first treatment with RAD001)
• HIV positive patients are not eligible; (HIV testing is not required for study entry; review of previous medical records is required)
• Uncontrolled hyperlipidemia (≥ Grade 3 hyperlipidemia despite optimal supportive medical therapy)
• Active, bleeding disorders or major surgery within 4 weeks of starting study drug
• Severe and/or uncontrolled medical conditions such as symptomatic congestive heart failure (NYHA Class III or IV), unstable angina, myocardial infarction within 6 months or study start, severely impaired lung function, cirrhosis, chronic active/persistent hepatitis.
• History of another primary malignancy ≤ 3 years prior to study entry