Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL
|Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Non-Hodgkin's Lymphoma||Drug: Fenretinide Drug: Cytarabine Drug: Methotrexate||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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"|
- Determine maximum tolerated dose [ Time Frame: end of study ]
- Define systemic toxicities [ Time Frame: end of study ]
- Determine plasma pharmacokinetics [ Time Frame: end of study ]
- Determine the response rate to IV Fenretinide [ Time Frame: end of study ]
- Determine bioavailability of fenretinide and metabolites [ Time Frame: 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.
|Study Start Date:||August 2010|
|Estimated Study Completion Date:||April 2018|
|Estimated Primary Completion Date:||April 2018 (Final data collection date for primary outcome measure)|
Experimental: Combination of Fenretinide, Cytarabine, and Methotrexate
IV for 7 days for each 21 day cycle
925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis.
Other Name: N-(4-hydroxyphenyl) retinamide, 4-HPRDrug: 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 Name: Ara-C, Cytosine Arabinoside, CytosarDrug: 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 Name: MTX, Amethopterin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01187810
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||Anna R Franklin, MD||M.D. Anderson Cancer Center|
|Study Chair:||Barry J Maurer, MD, PhD||Texas Tech University Health Sciences Center|
|Study Director:||Shengping Yang, PhD||Texas Tech University Health Sciences Center|
|Study Director:||Min Kang, PharmD||Texas Tech University Health Sciences Center|
|Study Director:||Patrick Reynolds, MD, PhD||Texas Tech University Health Sciences Center|