• Overall survival [ Designated as safety issue: No ]
• Progression-free survival [ Designated as safety issue: No ]
• Duration of response [ Designated as safety issue: No ]
• Laboratory measures [ Designated as safety issue: No ]
• Toxicity [ Designated as safety issue: Yes ]

• Overall survival
• Progression-free survival
• Duration of response
• Laboratory measures
• Toxicity

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking the enzymes necessary for their growth.

PURPOSE: This phase II trial is studying how well tipifarnib works in treating patients with relapsed or refractory lymphoma.

OBJECTIVES:

Primary

• Determine the tumor response in patients with relapsed or refractory non-Hodgkin's or Hodgkin's lymphoma treated with tipifarnib.
• Determine the toxicity of this drug in these patients.

Secondary

• Correlate known and unknown molecular markers with response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to histology (aggressive [closed to accrual as of 6/28/2006] vs indolent [closed to accrual as of 9/26/2007] vs uncommon).

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

Patients are followed every 6 months until disease progression and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 41-123 patients (12-41 with aggressive lymphoma [closed to accrual as of 6/28/2006], 17-41 with indolent lymphoma [closed to accrual as of 9/26/2007], and 12-41 with uncommon lymphoma) will be accrued for this study within 6-24 months.

• Leukemia
• Lymphoma

DISEASE CHARACTERISTICS:

• Histologically confirmed non-Hodgkin's or Hodgkin's lymphoma

  • Relapsed or refractory disease

  • The following histologies are eligible:

    • Aggressive lymphoma (closed to accrual as of 6/28/2006)

      • Transformed lymphoma
      • Diffuse large B-cell lymphoma
      • Mantle cell lymphoma
      • Grade 3 follicular lymphoma

    • Indolent lymphoma (closed to accrual as of 9/26/2007)

      • 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

      • Unspecified peripheral T-cell lymphoma
      • Anaplastic large cell lymphoma (T and null cell type)
      • Lymphoplasmacytic lymphoma
      • Mycosis fungoides/Sezary syndrome
      • Hodgkin's lymphoma
• Patients with aggressive lymphoma (closed to accrual as of 6/28/2006) OR Hodgkin's lymphoma must have received or be ineligible for potentially curative therapy, including stem cell transplantation

• Measurable disease, defined by 1 of the following:

  • At least one unidimensional lesion ≥ 2 cm in diameter
  • More than 5,000 tumor cells/mm^3 in the blood
• No CNS lymphoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm^3
• Platelet count ≥ 75,000/mm^3
• Hemoglobin ≥ 9 g/dL

Hepatic

• 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)

Renal

• Creatinine ≤ 2 times ULN

Other

• No other active malignancies
• No peripheral neuropathy ≥ grade 2
• No serious non-malignant disease that would preclude study participation
• No active infection
• No known allergy to imidazole drugs
• No other life-threatening illness unrelated to tumor
• Capable of swallowing intact study medication tablets
• Able to follow directions regarding study medications OR has a daily caregiver to administer study medication
• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• More than 3 weeks since prior biologic therapy
• No concurrent immunologic agents

Chemotherapy

• More than 3 weeks since prior myelosuppressive or cytotoxic chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• More than 2 weeks since prior corticosteroids for lymphoma
• Concurrent stable (not increased within the last month) chronic doses (maximum of 20 mg of prednisone daily) of corticosteroids for disorders other than lymphoma allowed

Radiotherapy

• At least 3 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery

• Not specified

Other

• No other concurrent cancer therapy
• No other concurrent cytotoxic agents