Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL

Phase 1

Terminated

• Conditions: Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Non-Hodgkin's Lymphoma
• Interventions: Drug: Fenretinide; Drug: Cytarabine; Drug: Methotrexate

• Registration Number: NCT01187810
• Lead Sponsor: South Plains Oncology Consortium

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.

Study Timeline

• Study Start: 2010-08
• Study First Submitted: 2010-08-23
• Study First Submitted QC: 2010-08-23
• Study First Posted: 2010-08-24
• Primary Completion: 2018-04
• Study Completion: 2018-04
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-17
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination of Fenretinide, Cytarabine, and Methotrexate	Fenretinide	IV for 7 days for each 21 day cycle
Combination of Fenretinide, Cytarabine, and Methotrexate	Cytarabine	IV for 7 days for each 21 day cycle
Combination of Fenretinide, Cytarabine, and Methotrexate	Methotrexate	IV for 7 days for each 21 day cycle

Primary Outcome Measures

Name	Time	Method
Determine plasma pharmacokinetics	end of study
Determine maximum tolerated dose	end of study
Define systemic toxicities	end of study

Secondary Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

University of Oklahoma Health Sciences Center; 🇺🇸 Oklahoma City, Oklahoma, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States