CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

PRIMARY OBJECTIVES:

I. Determine the complete and partial response rate in patients with recurrent or refractory B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia treated with CCI-779.

II. Determine the toxicity and safety of this drug in these patients. III. Correlate the degree of activation of P13/AKT/mTOR pathway and levels of CDK inhibitors with response in patients treated with this drug.

IV. Correlate CCI-779 induced inactivation of mTOR with response in these patients.

OUTLINE: Patients are stratified according to disease (aggressive lymphoma [group A] vs follicular lymphoma [group B] vs small lymphocytic lymphoma or chronic lymphocytic leukemia [group C]).

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 8 weeks.

Inclusion criteria

• Histologically or cytologically confirmed B-cell non-Hodgkin's lymphoma, including the following subtypes:

• Aggressive B-cell lymphoma (Group A)

• Diffuse large B-cell lymphoma
• Transformed lymphoma
• Follicular lymphoma (Group B)
• Small lymphocytic lymphoma

• Chronic lymphocytic leukemia (CLL) (Group C)
• Other B-cell small lymphocytic disorders
• No mantle cell lymphoma
• No potentially curative treatment options because of lack of response, relapse, or ineligibility
• Relapsed or refractory disease
• Patients with refractory disease (i.e., less than a partial response to the last treatment) must have received no more than 3 prior regimens (group A)
• Patients with sensitive disease (i.e., at least a partial response to the last treatment) must have received no more than 4 prior regimens (group A)
• Patients who have failed prior autologous transplantation are eligible (group A)

• No more than 5 prior regimens (groups B and C)
• The salvage regimen, conditioning regimen, and any maintenance therapy are considered 1 regimen
• Prior rituximab or alemtuzumab is not considered prior therapy
• No limitation to the amount of prior radiotherapy
• No CNS involvement
• Performance status: ECOG 0-2 OR Karnofsky 60-100%
• Life expectancy more than 3 months
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No prior allergic reactions attributed to compounds of similar chemical or biological composition to CCI-779
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other active malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix Completed therapy and considered < 30% risk of relapse
• No other concurrent uncontrolled illness
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent prophylactic hematopoietic colony-stimulating factors
• No concurrent pegfilgrastim
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• More than 4 weeks since prior radiotherapy and recovered
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent unconventional therapies, food, or vitamin supplements containing Hypericum perforatum (St. John's wort)
• No other concurrent known inducers of CYP3A4
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• Measurable disease*

• At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan [Note: *Only bone marrow or peripheral blood involvement required for CLL and Waldenstrom's macroglobulinemia ]
• Absolute neutrophil count >= 1,000/mm3
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• AST and ALT =< 2.5 times ULN
• Creatinine =< 1.5 times ULN
• Fasting cholesterol =< 350 mg/dL
• Fasting triglycerides =< 400 mg/dL
• Platelet count >= 50, 000/mm3 (> 20,000/mm3 for patients with thrombocytopenia due to bone marrow involvement)