Clinical trial NCT01187810: Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL
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"
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Non-Hodgkin's Lymphoma
Keywords: leukemia,lymphoma
Lead sponsor: South Plains Oncology Consortium
Sponsor class: NETWORK
First posted: 2010-08-24
Enrollment: 3
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Determine maximum tolerated dose
timeFrame: end of study
measure: Define systemic toxicities
timeFrame: end of study
measure: Determine plasma pharmacokinetics
timeFrame: end of study
Secondary outcomes:
measure: Determine the response rate to IV Fenretinide
timeFrame: end of study
measure: Determine bioavailability of fenretinide and metabolites
timeFrame: end of study
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Anna R Franklin, MD
role: STUDY_CHAIR
affiliation: Texas Tech University Health Sciences Center
name: Barry J Maurer, MD, PhD
role: STUDY_CHAIR
affiliation: Texas Tech University Health Sciences Center
name: Shengping Yang, PhD
role: STUDY_DIRECTOR
affiliation: Texas Tech University Health Sciences Center
name: Min Kang, PharmD
role: STUDY_DIRECTOR
affiliation: Texas Tech University Health Sciences Center
name: Patrick Reynolds, MD, PhD
role: STUDY_DIRECTOR
References: