• Maximum tolerated dose at 1 month [ Designated as safety issue: Yes ]
  
• Response rate [ Designated as safety issue: No ]
  

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