A Phase II Study of CCI-779 in B-cell Lymphoma and CLL

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)