Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL
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).
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: Yes ]
- Define systemic toxicities [ Time Frame: end of study ] [ Designated as safety issue: Yes ]
- Determine plasma pharmacokinetics [ Time Frame: end of study ] [ Designated as safety issue: No ]
- Determine the response rate to IV Fenretinide [ Time Frame: end of study ] [ Designated as safety issue: No ]
- Determine bioavailability of fenretinide and metabolites [ Time Frame: end of study ] [ Designated as safety issue: No ]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 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
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
|Contact: Amanda Knight, RN, BSNemail@example.com|
|Contact: Cory Rosas, LVN||806-743-2507 ext firstname.lastname@example.org|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center||Recruiting|
|Oklahoma City, Oklahoma, United States, 73104|
|Contact: Elaine Reeves 405-271-5849 email@example.com|
|Principal Investigator: William Meyer, MD|
|United States, Texas|
|MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Mary Tomaras, BS firstname.lastname@example.org|
|Principal Investigator: Anna R Franklin, MD|
|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:||Brad H Pollock, MPH, PhD||University of Texas Health Science Center, San Antonio|
|Study Director:||Min Kang, PharmD||Texas Tech University Health Sciences Center|
|Study Director:||Patrick Reynolds, MD, PhD||Texas Tech University Health Sciences Center|