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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by South Plains Oncology Consortium
Sponsor:
Information provided by (Responsible Party):
South Plains Oncology Consortium
ClinicalTrials.gov Identifier:
NCT01187810
First received: August 23, 2010
Last updated: June 6, 2014
Last verified: June 2014
  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:


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 2016
Estimated Primary Completion Date: April 2016 (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

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Amanda Knight, RN, BSN 806-743-2690 amanda.knight@ttuhsc.edu
Contact: Cory Rosas, LVN 806-743-2507 ext 309 cory.rosas@ttuhsc.edu

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: June 6, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by South Plains Oncology Consortium:
leukemia,lymphoma

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Lymphoma
Lymphoma, Non-Hodgkin
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cytarabine
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 22, 2014