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

NCT ID: NCT01187810

Last Updated: 2022-03-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2018-04-30

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination of Fenretinide, Cytarabine, and Methotrexate

IV for 7 days for each 21 day cycle

Group Type: EXPERIMENTAL

Fenretinide

Intervention Type: DRUG

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

Cytarabine

Intervention Type: DRUG

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

Methotrexate

Intervention Type: DRUG

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.

Interventions

Fenretinide

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

Intervention Type: 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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

N-(4-hydroxyphenyl) retinamide, 4-HPR; Ara-C, Cytosine Arabinoside, Cytosar; MTX, Amethopterin

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

• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

South Plains Oncology Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna R Franklin, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Barry J Maurer, MD, PhD

Role: STUDY_CHAIR

Texas Tech University Health Sciences Center

Shengping Yang, PhD

Role: STUDY_DIRECTOR

Texas Tech University Health Sciences Center

Min Kang, PharmD

Role: STUDY_DIRECTOR

Texas Tech University Health Sciences Center

Patrick Reynolds, MD, PhD

Role: STUDY_DIRECTOR

Texas Tech University Health Sciences Center

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

SPOC2008-01

Identifier Type: -

Identifier Source: org_study_id