Safety and Efficacy of RAD001 in Participants With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® Therapy

An Open-Label, Single-Arm, Phase II Study of RAD001 in Patients With Mantle Cell Lymphoma Who Are Refractory or Intolerant to Velcade® (Bortezomib)

This study was to evaluate the safety and efficacy of a daily, oral dose of 10 mg RAD001 in participants with Mantle Cell Lymphoma who were refractory or intolerant to Velcade® therapy and who had received at least one prior antineoplastic agent other than Velcade®, either separately or in combination with Velcade® (see inclusion criteria). Intolerance to Velcade® therapy was determined by the study investigator based on clinical evaluations. Participants were considered refractory to Velcade® if they have documented radiological progression on or within 12 months of the last dose of Velcade® when given alone or, on or within 12 months of the last dose of the last component of a combination therapy which included Velcade®.

Inclusion Criteria:

• Adult participants (≥18 years old) with Mantle Cell Lymphoma that has been confirmed by central pathology review (archival diagnostic tumor specimen required).
• Participants with mantle cell lymphoma who have documented refractory disease to Velcade® (bortezomib) or who have documented intolerance to Velcade® therapy. Intolerance to Velcade® is determined by the study investigator based on clinical evaluations. Participants 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®. Participants are considered refractory to Velcade®, if Velcade® is part of a combination treatment for the disease.
• Participants must have received at least one prior antineoplastic agent, other than Velcade® either separately or in combination with Velcade® (bortezomib).
• 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 computer tomography (CT) scan (or magnetic resonance imaging (MRI), only if CT scan can not be performed).
• Eastern Cooperative Oncology Group (ECOG) performance status = 0, 1 or 2.
• Life expectancy ≥3 months.
• Adequate bone marrow, liver and renal function.
• Platelets ≥75 x 10^9/L (untransfused platelets).

Exclusion Criteria:

• Participants 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 mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus, sirolimus, temsirolimus, etc).
• Participants 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.
• Participants with central nervous system (CNS) lymphoma are not eligible; head magnetic resonance imaging (MRI) (or computer tomography (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 participants are not eligible; (human immunodeficiency virus (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 (New York Heart Association 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.