Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Non-Hodgkin's Lymphoma
Conditions
Keywords
leukemia,lymphoma
Brief summary
The purposee of this study is to determine the safety and dosing of Fenretinide when given continuously for 5 days, every 3 weeks, in pediatric patients with recurrent and/or resistant acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and non-Hodgkin's lymphoma (NHL).
Detailed description
Fenretinide is a cytotoxic retinoid that has activity against a variety of cell lines in vitro in a dose-related manner. The exact mechanism of fenretinide cytotoxicity in leukemia and lymphoma cell lines is not known, but may include the de novo ceramide synthesis of ceramides and the generation of reactive oxygen species. The malignancy-specific nature of fenretinide-induced ceramides suggests that combinations of the drug with other ceramide modulating agents may have a favorable therapeutic index. In this study, the primary aims are to define the maximum tolerated dose, toxicity profile, and pharmacokinetics of IV fenretinide when given continuously in pediatric patients with ALL, AML, and NHL. The drug will be administered via a central venous or percutaneous indwelling central catheter in an inpatient hospital setting.
Interventions
DRUGFenretinide
925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis.
DRUGCytarabine
dosing depending on age - will be administed intrathecally for all CNS negative subjects on day 0 and 15 of course 1, then on day 8 of each remaining cycle for CNS negative AML. For CNS positive ALL, NHL, and AML, will be administered alone on day 0 for and in combination with methotrexate and hydrocortisone on day 8, 15, 22 of cycle 1 and repeated on day 8 of each remaining cycle
DRUGMethotrexate
Dose depends on subject age - for CNS positive patients, will be given in combination with cytarabine and hydrocortisone on days 8, 15, and 22 during course 1. For courses 2-6, will be administered intrathecally on day 8 for CNS negative ALL and NHL. For patients who are CNS positive, it will be given in combination with cytarabine and hydrocortisone on day 8 of courses 2-6.
Sponsors
South Plains Oncology Consortium
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosed with relapsed or refractory ALL, AML, or NHL * Must have had two or more therapeutic attempts for treating/curing disease * Must have fully recoved from acute toxic effects of all prior therapy * Karnofsky of greater than 50% for older than 10 years of age and Lansky greater than 50% for younger than 10 years.
Exclusion criteria
* Grade 2 Pruritus or Rash (all forms) * Grade 3 Dry Skin that is refractory to topical medical management * Cardiac Fractional Shortening \< 27% on echocardiogram * Left Ventricular Ejection Fraction \< 45% on echocardiogram * Known allergy to egg products or soy bean oil * Renal, Liver, and Pancreatic function: * serum creatinine \> 1.5X ULN * direct bilirubin \> 1.5X ULN * ALT or AST \> 2.5X ULN * Serum trigylcerides \> 2.5X ULN for age * Lipase \> 1.5X ULN for age * History of pancreatitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine maximum tolerated dose | end of study |
| Define systemic toxicities | end of study |
| Determine plasma pharmacokinetics | end of study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the response rate to IV Fenretinide | end of study | — |
| Determine bioavailability of fenretinide and metabolites | end of study | To determine the bioavailability to cancer or peripheral blood mononuclear cells (PBMC) cells of fenretinide and metabolites delivered/obtained as an intravenous emulsion. To determine alterations to sphingolipid levels in PBMC and/or circulating leukemia blasts induced by fenretinide. |
Countries
United States
Outcome results
None listed