Trial | NCT01187810  Report issue

Title

Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL
A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children With Recurrent or Resistant Acute Lymphoblastic Leukemia (ALL), Acute Myelogenous Leukemia (AML), and Non-Hodgkin's Lymphoma (NHL) IND #70,058"

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Terminated

  • Study Participants

    3
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).
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.
Study Started
Aug 31
2010
Primary Completion
Apr 30
2018
Study Completion
Apr 30
2018
Last Update
Mar 31
2022

Drug Fenretinide

925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis.

  • Other names: N-(4-hydroxyphenyl) retinamide, 4-HPR

Drug Cytarabine

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

  • Other names: Ara-C, Cytosine Arabinoside, Cytosar

Drug Methotrexate

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.

  • Other names: MTX, Amethopterin

Combination of Fenretinide, Cytarabine, and Methotrexate Experimental

IV for 7 days for each 21 day cycle

Criteria 

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
No Results Posted