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

March 17, 2022 updated by: South Plains Oncology Consortium

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"

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • University of Oklahoma Health Sciences Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination of Fenretinide, Cytarabine, and Methotrexate
IV for 7 days for each 21 day cycle
Drug: Fenretinide
925 mg/m2 IV continuous infusion X 5 days for 6 cycles. Dose escalation will occur on a 3X3 basis.
Other Names:
  • N-(4-hydroxyphenyl) retinamide, 4-HPR
Drug: 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 Names:
  • Ara-C, Cytosine Arabinoside, Cytosar
Drug: 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 Names:
  • MTX, Amethopterin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine maximum tolerated dose
Time Frame: end of study
end of study
Define systemic toxicities
Time Frame: end of study
end of study
Determine plasma pharmacokinetics
Time Frame: end of study
end of study

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the response rate to IV Fenretinide
Time Frame: end of study
end of study
Determine bioavailability of fenretinide and metabolites
Time Frame: 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.
end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

South Plains Oncology Consortium

Investigators

  • 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: Shengping Yang, PhD, Texas Tech University Health Sciences Center
  • Study Director: Min Kang, PharmD, Texas Tech University Health Sciences Center
  • Study Director: Patrick Reynolds, MD, PhD, Texas Tech University Health Sciences Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2010

Primary Completion (Actual)

April 1, 2018

Study Completion (Actual)

April 1, 2018

Study Registration Dates

First Submitted

August 23, 2010

First Submitted That Met QC Criteria

August 23, 2010

First Posted (Estimate)

August 24, 2010

Study Record Updates

Last Update Posted (Actual)

March 31, 2022

Last Update Submitted That Met QC Criteria

March 17, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPOC2008-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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