Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies
Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Hematologic Malignancies
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:
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:
Refractory or relapsed disease, as defined by 1 of the following:
No effective treatment exists
Measurable or evaluable disease
No active CNS disease
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
More than 2 weeks since prior chemotherapy except hydroxyurea
No other concurrent anticancer chemotherapy
Endocrine therapy
Radiotherapy
Surgery
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)
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:
No concurrent medications that may cause pseudotumor cerebri, including any of the following:
No concurrent medication to control hypertriglyceridemia
Los Angeles, California 90089-9181, United States
Bethesda, Maryland 20892-1182, United States