A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Inclusion Criteria:

- Histologically confirmed* mantle cell lymphoma (MCL)

- Relapsed, refractory, or stable disease after prior treatment

- Tumor must be cyclin D-1 by immunohistochemistry OR 11;14 translocation by
fluorescent in situ hybridization or cytogenetics

- Measurable disease, defined as ≥ 1 of the following:

- Unidimensionally measurable lymph node or tumor mass ≥ 2 cm by CT scan or MRI

- Splenic enlargement if spleen is palpable ≥ 3 cm below the left costal margin

- Malignant lymphocytosis if absolute lymphocytic count ≥ 5,000 AND lymphocytes
confirmed to be monoclonal by flow cytometry

- No known CNS involvement (e.g., parenchymal mass or leptomeningeal involvement)

- Performance status - ECOG 0-2

- At least 3 months

- No other concurrent treatment for MCL

- Absolute neutrophil count ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Direct bilirubin < 1.5 times ULN

- AST ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)

- Creatinine ≤ 2 times ULN

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Cholesterol ≤ 350 mg/dL

- Fasting triglycerides < 400 mg/dL

- No known HIV positivity

- No ongoing or active infection

- No psychiatric illness or social situation that would preclude study compliance

- No other uncontrolled illness

- No other active malignancy requiring treatment OR that would preclude assessment of
response to study drugs

- Prior biologic response modifiers allowed

- Prior immunotherapy allowed

- Prior high-dose therapy with stem cell support (i.e., stem cell transplantation)
allowed

- No concurrent prophylactic growth factor to support neutrophils

- Prior chemotherapy allowed

- No other concurrent chemotherapy

- No concurrent corticosteroids to induce an antitumor response

- Concurrent corticosteroids (≤ 10 mg/day of prednisone or equivalent) for
adrenal insufficiency or acute allergic reactions allowed

- Prior radiotherapy allowed

- No prior treatment with a mTOR inhibitor

- No other concurrent investigational or commercial agents or therapies for MCL

- No other concurrent immunosuppressive therapy