• 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.