CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

PRIMARY OBJECTIVES:

I. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.

II. Determine the tolerability of this regimen in these patients by assessing toxicity.

SECONDARY OBJECTIVES:

I. Determine the time to disease progression and overall survival of patients treated with this regimen.

II. Determine the duration of response in patients treated with this regimen.

OUTLINE: Patients are stratified according to prior response to rituximab (sensitive [partial response (PR) or complete response (CR) that lasted ≥ 6 months after the last treatment with rituximab alone or in combination with chemotherapy] vs refractory [stable or progressive disease OR a PR or CR that lasted < 6 months after the last treatment with rituximab alone or in combination with chemotherapy]).

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, and then annually for 2 years.

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 central nervous system involvement (e.g., parenchymal mass or leptomeningeal involvement)
• Performance status - Eastern Cooperative Oncology Group (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
• Aspartate aminotransferase (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 mammalian target of rapamycin (mTOR) inhibitor
• No other concurrent investigational or commercial agents or therapies for MCL
• No other concurrent immunosuppressive therapy