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

Primary Purpose

Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Fenretinide

Cytarabine

Methotrexate

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring leukemia,lymphoma

Eligibility Criteria

undefined - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Oklahoma Health Sciences Center
MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination of Fenretinide, Cytarabine, and Methotrexate

Arm Description

IV for 7 days for each 21 day cycle

Outcomes

Primary Outcome Measures

Determine maximum tolerated dose

Define systemic toxicities

Determine plasma pharmacokinetics

Secondary Outcome Measures

Determine the response rate to IV Fenretinide

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.

Full Information

NCT ID

NCT01187810

First Posted

August 23, 2010

Last Updated

March 17, 2022

Sponsor

South Plains Oncology Consortium

1. Study Identification

Unique Protocol Identification Number

NCT01187810

Brief Title

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

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Terminated

Why Stopped

drug supply

Study Start Date

August 2010 (undefined)

Primary Completion Date

April 2018 (Actual)

Study Completion Date

April 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

South Plains Oncology Consortium

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Non-Hodgkin's Lymphoma

Keywords

leukemia,lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combination of Fenretinide, Cytarabine, and Methotrexate

Arm Type

Experimental

Arm Description

IV for 7 days for each 21 day cycle

Intervention Type

Drug

Intervention Name(s)

Fenretinide

Other Intervention Name(s)

N-(4-hydroxyphenyl) retinamide, 4-HPR

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cytarabine

Other Intervention Name(s)

Ara-C, Cytosine Arabinoside, Cytosar

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Other Intervention Name(s)

MTX, Amethopterin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Determine maximum tolerated dose

Time Frame

end of study

Title

Define systemic toxicities

Time Frame

end of study

Title

Determine plasma pharmacokinetics

Time Frame

end of study

Secondary Outcome Measure Information:

Title

Determine the response rate to IV Fenretinide

Time Frame

end of study

Title

Determine bioavailability of fenretinide and metabolites

Description

Time Frame

end of study

10. Eligibility

Sex

All

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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

Overall Study Officials: