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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01187810
Recruitment Status : Terminated (drug supply)
First Posted : August 24, 2010
Last Update Posted : March 31, 2022
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Non-Hodgkin's Lymphoma Drug: Fenretinide Drug: Cytarabine Drug: Methotrexate Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : August 2010
Actual Primary Completion Date : April 2018
Actual Study Completion Date : April 2018

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 Name: 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 Name: 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 Name: MTX, Amethopterin

Primary Outcome Measures :
  1. Determine maximum tolerated dose [ Time Frame: end of study ]
  2. Define systemic toxicities [ Time Frame: end of study ]
  3. Determine plasma pharmacokinetics [ Time Frame: end of study ]

Secondary Outcome Measures :
  1. Determine the response rate to IV Fenretinide [ Time Frame: end of study ]
  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01187810

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United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
South Plains Oncology Consortium
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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
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Responsible Party: South Plains Oncology Consortium Identifier: NCT01187810    
Other Study ID Numbers: SPOC2008-01
First Posted: August 24, 2010    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by South Plains Oncology Consortium:
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors