This phase II trial studies how well tipifarnib works in treating patients with relapsed or refractory non-Hodgkin's lymphoma. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Tipifarnib may be an effective treatment for non-Hodgkin's lymphoma.

PRIMARY OBJECTIVES:

I. To assess tumor response to R115777 (tipifarnib) in patients with relapsed aggressive non-Hodgkin's lymphoma. (Permanently closed to accrual 6/28/06) II. To assess tumor response to R115777 in patients with relapsed indolent non-Hodgkin's lymphoma. (Permanently closed to accrual 9/26/07) III. To assess tumor response to R115777 in patients with uncommon non-Hodgkin's lymphomas.

IV. To evaluate toxicity associated with this regimen in patients with relapsed non-Hodgkin's lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate known and unknown molecular markers that may predict for response to R115777 in lymphoma tissue.

OUTLINE:

Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 2 years.

Inclusion Criteria:

• Biopsy-proven relapsed or refractory lymphomas; previous biopsies =< 6 months prior to treatment on this protocol will be acceptable as long as there has not been intervening therapy; if the patient has received therapy for non-Hodgkin's disease (NHL) between the time of the last biopsy and this protocol, then a re-biopsy is necessary

• STUDY 1: Aggressive lymphomas (permanently closed to accrual 6/28/06):

  • Transformed lymphomas
  • Diffuse large B cell lymphoma
  • Mantle cell lymphoma
  • Follicular lymphoma grade III STUDY 2: Indolent lymphomas (permanently closed to accrual 9/26/07)
  • Small lymphocytic lymphoma/chronic lymphocytic leukemia
  • Follicular lymphoma, grades 1, 2
  • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type
  • Nodal marginal zone B-cell lymphoma
  • Splenic marginal zone B-cell lymphoma

STUDY 3: Uncommon lymphomas:

• Peripheral T cell lymphoma, unspecified

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

• Lymphoplasmacytic lymphoma

• Mycosis fungoides/ Sezary syndrome

• Relapsed Hodgkin's disease (patients must be previously treated and either have had a transplant or not be eligible for a transplant)

  • Previously treated (no limitations on the number of prior therapies); patients with aggressive lymphoma (Study 1 - permanently closed to accrual 6/28/06) should have received or be ineligible for potentially curable therapy including stem cell transplant
  • MEASURABLE DISEASE: Must have at least one lesion that has a single diameter of >= 2 cm or tumor cells in the blood >= 5 x10^9/L
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count >=1000/mm^3
  • Platelet count >= 75,000
  • Hemoglobin >= 9 g/dL
  • Total bilirubin =< 2 x upper limit of normal (ULN) (if > 2 x ULN direct bilirubin is required and should be =< 1.5 x ULN)
  • Aspartate aminotransferase (AST) =< 3 x ULN (=< 5 x ULN if liver involvement is present)
  • Serum creatinine =< 2 x ULN
  • Expected survival >= 3 months
  • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent
  • Capable of swallowing intact study medication tablets
  • Capable of following directions regarding taking study medication, or has a daily caregiver who will be responsible for administering study medication

Exclusion Criteria:

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:

  • Pregnant women
  • Breastfeeding women
  • Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.)
  • NOTE: The effects of R115777 on the developing human fetus at the recommended therapeutic dose are unknown

• Life-threatening illness (unrelated to tumor)

• Ongoing radiation therapy or radiation therapy =< 3 weeks prior to study registration unless the acute side effects associated with such therapy are resolved

• Therapy with myelosuppressive chemotherapy, cytotoxic chemotherapy, or biologic therapy =< 3 weeks (6 weeks for nitrosourea or mitomycin C) or corticosteroids =< 2 weeks, prior to starting R11577; patients may be on corticosteroids or tapering off them up until the day they start R11577 as long as it is clear that they are not having a tumor response to the steroids or that the steroids would confuse the interpretation of response to R11577; patients may be receiving stable (not increased within the last month) chronic doses of corticosteroids with a maximum dose of 20 mg of prednisone per day if they are being given for disorders other than lymphoma such as rheumatoid arthritis, polymyalgia rheumatica, adrenal insufficiency, or intractable symptoms of lymphoma

• Peripheral neuropathy >= grade 3

• Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives

• Presence of central nervous system (CNS) lymphoma

• Other active malignancies

• Once a patient begins FTI (tipifarnib) treatment, the addition of other cancer treatment will confound the assessment of efficacy and therefore is not allowed; this restriction precludes the addition of cytotoxic, immunologic agents, radiotherapy, or an increase in corticosteroid dose while the patient is in the treatment phase of this protocol

• Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV patients are excluded because of concerns regarding excess risk of complications of immunosuppressive therapy regimens

• Known allergy to imidazole drugs such as clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, sulconazole, tioconazole, or terconazole