Everolimus in Treating Patients With Lymphoma That Has Relapsed or Not Responded to Previous Treatment

OBJECTIVES:

Primary

- Assess the tumor response in patients with relapsed or refractory indolent non-Hodgkin
lymphoma (closed to accrual as of 8/18/08), aggressive non-Hodgkin's lymphoma (closed to
accrual as of 2/7/08 except for diffuse large B cell lymphoma, grade III follicular
lymphoma, or transformed lymphoma), or uncommon lymphoma (closed to accrual as of
9/2/08), including Hodgkin's lymphoma, treated with everolimus.

Secondary

- Evaluate overall survival, progression-free survival, and time to disease progression in
patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology
(aggressive lymphoma [closed to accrual as of 2/7/08 except for diffuse large B cell
lymphoma, grade III follicular lymphoma, or transformed lymphoma] vs indolent lymphoma
[closed to accrual as of 8/18/08] vs uncommon lymphoma [closed to accrual as of 9/2/08]).

Patient receive oral everolimus daily on days 1-28. Treatment repeats every 28 days in the
absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue collection at baseline and periodically during study
treatment for translational research studies. Blood and tissue samples are analyzed for
biomarkers to study the effect of everolimus on lymphoma.

After completion of study treatment, patients are followed periodically for up to 5 years.

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)

- Central Nervous System (CNS) lymphoma

- Post-transplant lymphoproliferative disorder

- Mycosis fungoides/Sezary syndrome

- Hodgkin's lymphoma

- Primary effusion lymphoma

- Blastic Natural Killer(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 Immunoglobulin M(IgM)
monoclonal protein > 1,000 mg/dL

PATIENT CHARACTERISTICS:

- Eastern Cooperative Oncology Group(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

- aspartate aminotransferase(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