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

Acute Lymphoblastic Leukemia Clinical Trial

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"

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01187810
• Other study ID #: SPOC2008-01
• Status: Terminated
• Phase: Phase 1
• Start date: August 2010
• Est. completion date: April 2018

Study information

• Verified date: March 2022
• Source: South Plains Oncology Consortium
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: April 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myelogenous Leukemia
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
South Plains Oncology Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine maximum tolerated dose		end of study
Primary	Define systemic toxicities		end of study
Primary	Determine plasma pharmacokinetics		end of study
Secondary	Determine the response rate to IV Fenretinide		end of study
Secondary	Determine bioavailability of fenretinide and metabolites	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.	end of study