Trial of Intravenous Fenretinide Emulsion for Patients With Relapsed/Refractory Peripheral T-cell Lymphomas

Inclusion Criteria:

• Adult patients > 18 years with histologically or cytologically confirmed PeripheralT-cell lymphoma (PTCL)

• Diseases refractory/relapsed after one or more systemic cytotoxic therapies; patientsmust have fully recovered from the acute toxic effects of all prior chemotherapy,immunotherapy, or radiotherapy prior to entering this study.

• Patients with an ECOG performance status of 0, 1, or 2, and estimated survival of > 12weeks.

• Patients with at least ONE of the following sites of measurable disease according toInternational Workshop Criteria87: A) Measurable tumor on MRI or CT scan. Measurableis defined as at least one lesion 20 mm in at least one dimension; for spiral CT,measurable is defined as 10 mm in at least one dimension. For patients with persistentdisease, a biopsy of bone marrow, or bone, or a soft tissue site, must havedemonstrated viable tumor. If lesion was radiated, biopsy must have been done at least 4 weeks after radiation completed. B) Bone marrow with tumor cells seen on routinemorphology (not by NSE staining only) of bilateral aspirate and/or biopsy on one bonemarrow sample, except for patient who tested positive subsequent to their lasttreatment regimen or patients who had a negative marrow within three months of studyentry.

Exclusion Criteria:

• Unable to give written informed consent

• Patients who have received chemotherapy within 3 weeks of first fenretinide treatment,or who have received investigational drugs within 6 weeks of first fenretinidetreatment. Patients must have otherwise recovered from toxicities of prior therapy.

• Patient is not eligible if radiation was given to the only site of measurable diseaseunless there has been subsequent disease progression at that site, or a biopsy of thatsite showed viable tumor at least 4 weeks after radiation was completed. Patients mustnot have received small field (focal) radiation for a minimum of 2 weeks prior tostudy entry. A minimum of 6 weeks is required following prior large field radiationtherapy (i.e. TBI, craniospinal therapy, whole abdomen, total lung, > 50% marrowspace)

• Patients who have uncontrolled systemic infections, coagulation disorders, or othermajor medical illnesses of the cardiovascular or respiratory systems.

• Patients with any active hepatitis infections.

• Growth factor(s): Must not have received any hematopoetic growth factors within 7 daysof study entry.

• Organ Transplant: Patients may NOT be the recipients of an organ transplant.

• Women who are pregnant and/or lactating.

• Patients who have had major non-biopsy surgery in the last 20 days.

• CNS lesions: A) Patients with CNS parenchymal or meningeal-based lesions that arepresent at study entry are NOT eligible due to concerns regarding toxicityattribution. B) Who have active CNS disease or a history of cranial irradiation areexcluded due to concerns regarding toxicity attribution. Patients with previouslytreated leptomeningeal disease or brain metastases without evidence of remaining tumorby PET, MRI scan, or spinal fluid will be eligible; however such patients currentlytaking steroids as prophylaxis against seizures are not eligible.

• Patients with documented allergy to egg products.

• Known history of, or positive test result for human immunodeficiency virus (HIV)infection.

• Patients with fasting serum triglycerides > 300 and/or with hypertriglyceridemiarequiring medication (but not patients with hypercholesterolemia: patients withhypercholesterolemia with or without medication are eligible).

• Patients concurrently taking the following drugs are excluded: antioxidants, herbal orother alternative therapy medications, vitamin supplements (especially vitamins A, C,and E) other than at standard multivitamin doses, cyclosporine A or analogue;verapamil; tamoxifen or analogue, ketoconazole, chlorpromazine; RU486; indomethacin;or sulfinpyrazone, tetracycline, nalidixic acid, nitrofurantoin, phenytoin,sulfonamides, lithium, and amiodarone. If the patients discontinue usage of the abovedrugs, they can be eligible for enrollment into the study (screening visit) one weekor 5-half lives of the drug in question, whichever is the longer, after thediscontinuation. For patients requiring any of these medications, entry is permissibleonly with permission from the medical monitor.

• Patients with poorly controlled diabetes mellitus with fasting serum glucoseconcentration over 200 mg/dl or a hemoglobin A1C over 7.5%.

• Patients with any known significant cardiac abnormality.

• Patients with uncontrolled hypertension.

• Participation in any other investigational treatment within the 6 weeks prior toenrollment or concurrent with this study.

• Patients with an identified familial hyperlipidemia disorder.

• Patients with documented allergy to soy products.