Fenretinide in Children With Recurrent/Resistant ALL, AML, and NHL - Full Text View

Purpose

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	Intervention	Phase
Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia Non-Hodgkin's Lymphoma	Drug: Fenretinide Drug: Cytarabine Drug: Methotrexate	Phase 1

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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"

Resource links provided by NLM:

Genetics Home Reference related topics: familial acute myeloid leukemia with mutated CEBPA

MedlinePlus related topics: Acute Myeloid Leukemia Chronic Lymphocytic Leukemia Leukemia Lymphoma

Drug Information available for: Methotrexate Cytarabine Methotrexate sodium

U.S. FDA Resources

Further study details as provided by South Plains Oncology Consortium:

Primary Outcome Measures:

Determine maximum tolerated dose [ Time Frame: end of study ] [ Designated as safety issue: Yes ]
Define systemic toxicities [ Time Frame: end of study ] [ Designated as safety issue: Yes ]
Determine plasma pharmacokinetics [ Time Frame: end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Determine the response rate to IV Fenretinide [ Time Frame: end of study ] [ Designated as safety issue: No ]
Determine bioavailability of fenretinide and metabolites [ Time Frame: end of study ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	18
Study Start Date:	August 2010
Estimated Study Completion Date:	April 2014
Estimated Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Fenretinide	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

Arms

Assigned Interventions

Experimental: Fenretinide

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

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

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01187810

Locations

United States, Oklahoma
University of Oklahoma Health Sciences Center	Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Elaine Reeves 405-271-5849 elaine-reeves@ouhsc.edu
Principal Investigator: William Meyer, MD
United States, Texas
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Mary Tomaras, BS mtomaras@mdanderson.org
Principal Investigator: Anna R Franklin, MD

Sponsors and Collaborators

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:	Brad H Pollock, MPH, PhD	University of Texas Health Science Center, San Antonio
Study Director:	Min Kang, PharmD	Texas Tech University Health Sciences Center
Study Director:	Patrick Reynolds, MD, PhD	Texas Tech University Health Sciences Center

More Information

No publications provided

Responsible Party:	South Plains Oncology Consortium
ClinicalTrials.gov Identifier:	NCT01187810 History of Changes
Other Study ID Numbers:	SPOC2008-01
Study First Received:	August 23, 2010
Last Updated:	February 3, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by South Plains Oncology Consortium:

leukemia,lymphoma

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Methotrexate

Fenretinide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on May 23, 2013