Phase II Trial of RAD001 in Relapsed/Refractory Lymphoma

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Biopsy-proven* relapsed or refractory lymphoma, including the following:

- Aggressive lymphoma (closed to accrual as of 2/7/08 except for diffuse large B
cell lymphoma, grade III follicular lymphoma, or transformed lymphoma)

- Transformed lymphoma

- Diffuse large B-cell lymphoma

- Mantle cell lymphoma

- Grade 3 follicular lymphoma

- Precursor B-cell lymphoblastic leukemia/lymphoma

- Mediastinal (thymic) large B-cell lymphoma

- Burkitt's lymphoma/leukemia

- Precursor T-cell lymphoblastic leukemia/lymphoma

- Primary cutaneous anaplastic large cell lymphoma

- Primary systemic type anaplastic large cell lymphoma

- Indolent lymphoma (closed to accrual as of 8/18/08)

- Small lymphocytic lymphoma/chronic lymphocytic leukemia

- Grade 1 or 2 follicular lymphoma

- Extranodal marginal zone B-cell lymphoma of MALT type

- Nodal marginal zone B-cell lymphoma

- Splenic marginal zone B-cell lymphoma

- Uncommon lymphoma (closed to accrual as of 9/2/08)

- Unspecified peripheral T-cell lymphoma

- Anaplastic large cell lymphoma (T and null cell type)

- Lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia)

- CNS lymphoma

- Post-transplant lymphoproliferative disorder

- Mycosis fungoides/Sezary syndrome

- Hodgkin's lymphoma

- Primary effusion lymphoma

- Blastic NK-cell lymphoma

- Adult T-cell leukemia/lymphoma

- Nasal type extranodal NK/T-cell lymphoma

- Enteropathy type T-cell lymphoma

- Hepatosplenic T-cell lymphoma

- Subcutaneous panniculitis-like T-cell lymphoma

- Angioimmunoblastic T-cell lymphoma NOTE: *Biopsies performed < 6 months
prior to study entry are allowed; biopsy-proven CNS lymphoma (at any time)
does not require a re-biopsy in order to be eligible for this study

- Previously treated disease

- Patients with aggressive lymphoma (closed to accrual as of 8/24/07) OR Hodgkin's
lymphoma must have received or be ineligible for potentially curative therapy,
including stem cell transplantation

- Measurable disease** by CT scan or MRI, defined by 1 of the following:

- At least 1 unidimensionally measurable lesion > 2 cm in diameter

- Skin lesions may be used if they meet this criterion and are photographed
with a ruler

- More than 5,000/mm³ tumor cells in the blood NOTE: **For patients with
lymphoplasmacytic lymphoma without measurable lymphadenopathy, measurable
disease may be defined by bone marrow lymphoplasmacytosis with > 10%
lymphoplasmacytic cells or aggregates, sheets, lymphocytes, plasma cells, or
lymphoplasmacytic cells on bone marrow biopsy AND quantitative IgM monoclonal
protein > 1,000 mg/dL

PATIENT CHARACTERISTICS:

- ECOG performance status 0-2

- Life expectancy > 3 months

- Absolute neutrophil count ≥ 1,000/mm³

- Platelet count ≥ 75,000/mm³

- Hemoglobin ≥ 8 g/dL

- Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times
ULN

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

- Creatinine ≤ 2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Willing to provide blood samples and portion of bone marrow aspirate and biopsy
during study participation

- Able to swallow intact study medication tablets

- No other life-threatening illness (unrelated to tumor)

- No serious non-malignant disease (e.g., active infection or other condition) that, in
the opinion of the investigator, would preclude study participation

- No other active malignancy requiring treatment or that would preclude study
participation

- No known HIV positivity

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 3 weeks since prior myelosuppressive chemotherapy or biologic therapy
(unless the patient has recovered from the nadir of the previous treatment)

- More than 3 weeks since prior radiotherapy (unless the acute side effects associated
with therapy are resolved)

- Concurrent stable (i.e., not increased within the past month) chronic doses of
corticosteroids, with a maximum dose of 20 mg of prednisone per day, is allowed if
prescribed for disorders other than lymphoma (e.g., rheumatoid arthritis, polymyalgia
rheumatica, adrenal insufficiency, or asthma)

- Non-escalating doses of steroids at the lowest possible dosing level are allowed
for CNS lymphoma

- No other concurrent investigational ancillary therapy

- No other concurrent chemotherapy, immunotherapy, or radiotherapy

- No concurrent participation in any other clinical trial involving a pharmacologic
agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or
therapeutic intent