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. Giving fenretinide in a different way may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating patients with refractory or relapsed hematologic cancer.

OBJECTIVES:

• Determine the maximum tolerated dose of intravenous emulsified fenretinide in patients with refractory or relapsed hematologic malignancies.
• Determine the toxic effects of this drug in these patients.
• Determine the pharmacokinetics and in vivo activity of this drug in these patients.
• Determine, preliminarily, disease or tumor response in patients treated with this drug.

OUTLINE: This is a pilot, dose-escalation, multicenter study.

Patients receive emulsified fenretinide IV continuously over 5 days. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete or partial response may continue to receive fenretinide at the discretion of the study chair.

Cohorts of 1 patient receive accelerated escalating doses of fenretinide until 2 patients experience moderate toxicity (cumulative across all dose levels) OR 1 patient experiences dose-limiting toxicity (DLT). After completion of the accelerated dose-escalation portion, the standard dose-escalation portion begins. 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 DLT. At least 6 patients are treated at the MTD. An additional 12 patients are treated at the MTD.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following hematologic malignancies:

  • Non-Hodgkin's lymphoma (NHL)

  • Hodgkin's lymphoma

  • Multiple myeloma

  • Acute lymphoblastic leukemia

  • Acute myeloid leukemia

  • Chronic hematologic malignancy with a poor prognosis (e.g., failed 3 prior standard therapies), including any of the following:

    • Chronic lymphocytic leukemia
    • Chronic myelogenous leukemia
    • Indolent NHL
    • Myeloproliferative disorders

• Refractory or relapsed disease, as defined by 1 of the following:

  • Resistant to standard therapy for refractory or relapsed disease
  • Progressed after standard therapy for advanced disease

• No effective treatment exists

• Measurable or evaluable disease

• No active CNS disease

  • Previously treated leptomeningeal disease or brain metastases allowed provided there is no evidence of remaining cancer by positron-emission tomography, MRI, or spinal fluid cytology

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3 (unless due to bone marrow involvement of disease)
• Platelet count ≥ 75,000/mm^3 (unless due to bone marrow involvement of disease)
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
• No coagulation disorders

Hepatic

• AST and ALT < 2.5 times upper limit of normal (ULN) (≤ 5 times ULN for patients with liver metastasis)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No major cardiovascular disease

Pulmonary

• No major respiratory disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-method contraception prior to study entry, during study, and for at least 6 months after study participation
• No uncontrolled systemic infection
• No uncontrolled hypertriglyceridemia (i.e., triglyceride level > 500 mg/dL)
• No known HIV positivity
• No known allergy to egg products
• No known familial hyperlipidemia disorders
• No previously undiscovered hypertriglyceridemia
• No poorly controlled diabetes

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• More than 2 weeks since prior chemotherapy except hydroxyurea

  • No concurrent hydroxyurea during study drug administration

• No other concurrent anticancer chemotherapy

Endocrine therapy

• No concurrent hormone-ablative agents
• No concurrent steroids
• No concurrent tamoxifen or any of its analogues

Radiotherapy

• No prior cranial radiotherapy
• More than 2 weeks since prior radiotherapy

Surgery

• More than 20 days since prior surgery except for biopsy

Other

• Recovered from all prior therapy

• More than 2 weeks since prior investigational agents

• No other concurrent investigational agents

• No other concurrent antineoplastic therapy

• No other concurrent antioxidants

• No concurrent herbal or other alternative therapies

• No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)

  • Standard dose multivitamin allowed

• No other concurrent medications that may act as modulators of intracellular ceramide levels or ceramide cytotoxicity, sphingolipid transport, or p-glycoprotein or multidrug resistance protein 1 (MRP1) drug/lipid transporters, including any of the following:

  • Cyclosporine or any of its analogues
  • Verapamil
  • Ketoconazole
  • Chlorpromazine
  • Mifepristone
  • Indomethacin
  • Sulfinpyrazone

• No concurrent medications that may cause pseudotumor cerebri, including any of the following:

  • Tetracycline
  • Nalidixic acid
  • Nitrofurantoin
  • Phenytoin
  • Sulfonamides
  • Lithium
  • Amiodarone

• No concurrent medication to control hypertriglyceridemia