Fever and Neutropenia in Pediatric Oncology Patients

Fever and Neutropenia in Pediatric Oncology Patients: A Randomized, Controlled, Multi-Center Study of Outpatient Therapy Evaluation of Genomic and Proteomic Correlates

It is possible to distinguish between pediatric oncology patients who are at high or low risk for serious infection during periods of fever and treatment related neutropenia based on clinical parameters. Patients with low risk can be safely treated as outpatients primarily using oral antibiotics. It is possible to improve methods of risk stratification through the addition of genomic and proteomic factors.

Study Overview

• Status: Withdrawn
• Conditions: Neutropenia; Fever
• Intervention / Treatment: Drug: Low Risk: Oupatient Management; Drug: Low Risk: Inpatient Management; Drug: High Risk: Inpatient Management

Detailed Description

Outpatient management of patients considered to be at low risk for serious bacterial infection has been explored using risk stratification schema based on clinical parameters. First, patients will be stratified based on a clinical risk stratification schema. Patients stratified to the low risk group will be randomized between treatment using standard inpatient intravenous antibiotic therapy or outpatient antibiotic therapy using primarily an oral regimen. Second, an evaluation of proteins important to the innate immune system will be performed to provide a molecular characterization of episodes based on etiology. Third, single nucleotide polymorphisms in genes important for innate immunity will be evaluated to determine effect of each on infection risk during treatment induced neutropenia. Finally, we will develop a bank of both plasma and DNA specimens correlated with clinical outcomes for future use.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Any pediatric patient age <21 years with an oncology diagnosis who is undergoing therapy and is expected to have treatment related neutropenia.

Exclusion Criteria:

1. Any patient who has previously undergone autologous or allogeneic bone marrow transplant will be excluded from study enrollment. If a patient is expected to undergo autologous or allogeneic bone marrow transplant as part of therapy at some point after enrollment in the study he/she will be removed from the study at the start of their bone marrow transplant.
2. Any patient with a documented allergy to Levofloxacin or any other fluoroquinolone will be excluded.
3. Patients with a known pregnancy will be excluded.
4. Any patient with an underlying chronic musculoskeletal condition (ie Juvenile rheumatoid arthritis, Systemic lupus erythematosis etc) which may make evaluation for joint toxicity related to quinolone treatment difficult.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Low Risk: Oupatient Management; Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.	Drug: Low Risk: Oupatient Management; Intravenous Levaquin initially, then oral dosing. Patient discharged to go home to finish medication cycle after initial 120 minutes observation. Patients will be evaluated daily in the clinic, and his or her temperature must be taken and recorded four times per day. Blood cultures will be drawn at clinic visits.; Other Names: Oral Antibiotics
ACTIVE_COMPARATOR: Low Risk: Inpatient Management; Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.	Drug: Low Risk: Inpatient Management; Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.; Other Names: IV Antibiotics
ACTIVE_COMPARATOR: High Risk: Inpatient Management; Patients will be categorized according to risk of serious bacterial infection per risk stratification system, which is based on demographic, clinical history and physical findings that have been shown to be predictive of risk.	Drug: High Risk: Inpatient Management; Broad spectrum intravenous antibiotics. Daily blood work will be drawn, and patients will be monitored for fever and neutropenia in hospital.; Other Names: IV Antibiotics, High Risk

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low Risk Treatment	The response to initial antibiotic management without modification with regards to resolution of the episode of fever and neutropenia, measured through blood cultures	Start of study to end of study, up to two years
Protein Evaluation	Comparison of the level of each protein at the initiation of each episode versus resolution to determine if there is a pattern of proteins that correlates with an infectious outcome, measured using ELISA techniques	Start of study to end of study, up to two years
Genomics Evaluation	A comparison of proven infections between patients with the wild-type and variant forms of each gene studied, taken through DNA specimens	Start of study to end of study, up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost Benefit Analysis	A cost-benefit analysis between the arms, duration of fever per episode between the arms, and number of admissions or deaths. Medical cost will be obtained through billing records and indirect costs will be estimated through information obtained from the family.	Start of study to end of study, up to two years
Protein Evaluation	Determine trends of protein markers on days 3 and 5 of evaluation, using ELISA techniques.	Start of study to end of study, up to two years
Genomics Evaluation	A comparison of the number of episodes of fever and neutropenia per patient and the duration of fever per episode between the wild type and variant forms of each gene, taken through DNA specimens.	Start of study to end of study, up to two years

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Kelly Maloney, MD, Children's Hospital Colorado

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2006
• Primary Completion (ACTUAL): April 3, 2009
• Study Completion (ACTUAL): April 3, 2009

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (ACTUAL): December 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Pediatrics; Oncology; Outpatient therapy
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Neutropenia; Fever; Anti-Infective Agents; Antitubercular Agents; Anti-Bacterial Agents; Antibiotics, Antitubercular
• Other Study ID Numbers: 05-0300.cc

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No