RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Giving fenretinide together with rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of fenretinide and to see how well it works when given together with rituximab in treating patients with B-cell non-Hodgkin's lymphoma.

OBJECTIVES:

Primary

• Evaluate the safety of fenretinide in patients with B-cell non-Hodgkin's lymphoma. (phase I)
• Estimate the efficacy (response rates) of fenretinide and rituximab in these patients. (phase II)

Secondary

• Determine the response rates, positron emission tomography response, overall survival, progression-free survival, time to progression, and disease-free survival of these patients.
• Determine the pharmacokinetics of fenretinide in these patients.
• Determine the intratumoral concentration of fenretinide.
• Evaluate the in vivo mechanism of action of fenretinide in these patients.
• Identify the predictors of response to fenretinide and fenretinide plus rituximab in these patients.

OUTLINE: This is a phase I, dose-escalation study of fenretinide followed by a phase II study of fenretinide and rituximab.

• Phase I: Patients receive oral fenretinide twice daily on days 1-5. Treatment repeats weekly for at least 4 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

• Phase II: Patients receive oral fenretinide at the MTD twice daily on days 1-5. Treatment repeats weekly for at least 8 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV on days 32, 39, 46, and 53 and then once every 3 months (after month 3) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 3 and 6 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 52 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Confirmed B-cell non-Hodgkin's lymphoma

  • Confirmed CD20-positive disease
• WHO classification of patient's malignancy must be provided

• Measurable disease defined as lesions that can be accurately measured in 2 dimensions by CT scan, MRI, medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters ≥ 2 cm OR evaluable disease in the bone marrow

  • Radiographically measurable disease not required for chronic lymphocytic leukemia
• Patients with evidence of adenopathy in the neck must have a CT scan of the neck
• No evidence of active CNS malignancy

PATIENT CHARACTERISTICS:

• SWOG/ECOG performance status ≤ 2
• Expected survival (if untreated) of ≥ 60 days
• Bilirubin < 2 times upper limit of normal (ULN)
• Creatinine < 2 times ULN
• No other serious condition
• No known HIV positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• At least 28 days since prior anticancer therapy
• No other concurrent antineoplastic therapy
• No concurrent ascorbic acid, vitamin A derivatives, vitamin E, or other antioxidants