The purpose of this study is to determine whether, in children with cancer presenting with fever in severe chemotherapy-induced neutropenia at low risk for medical complications, oral antibiotics in an outpatient setting after an initial phase of intravenous antibiotics and in-hospital observation for 8 to 22 hours, is not inferior as to safety and efficacy compared to continued intravenous antibiotics given in-hospital.

Condition	Treatment or Intervention	Phase
Fever Neutropenia Cancer	Drug: ciprofloxacin and amoxicillin  Procedure: Outpatient management	Phase III

Further Study Details: 

Primary Outcomes: Safety: No serious medical complication due to infection (death, treatment in ICU [Intensive Care Unit], potentially life-threatening complication) (non-inferiority-design, limit 3.5%); Efficacy: Response without rehospitalization or changing randomized antibiotics (non-inferiority design, limit 10%)
Secondary Outcomes: Improved prediction of low-risk episodes of fever and neutropenia; Description of characteristics of low-risk episodes of fever and neutropenia; Description of characteristics of high-risk episodes of fever and neutropenia (observational study part)
Expected Total Enrollment:  360

Details on antimicrobial therapy

• At presentation with FN (fever and neutropenia) and during an initial inpatient observation period of 8 to 22 hours, empirical intravenous broad-spectrum antibiotics are given. Type and dosage are chosen by the treating physician.
• Patients randomized to continued intravenous antibiotics continue with these antibiotics.
• Patients randomized to oral antibiotics receive a combination of oral ciprofloxacin (25 to 30 mg/kg/day, top dose 1500 mg/day) plus oral amoxicillin (65 to 80 mg/kg/day, top dose 2250 mg/day), both given in two doses per day.
• In both groups, the study gives guidelines (for certain situations) and rules (for other situations) when to change and when to stop antibiotics.

Details on clinical and laboratory controls

• During antibiotic therapy, patients are seen daily, either as inpatients or as outpatients according to randomization. Complete blood counts are performed at least every second day.
• After stopping antibiotic therapy and until resolution of severe neutropenia (if applicable), patients are seen every other day, with a complete blood count.
• Patients randomized to outpatient management have the possibility to contact at any time of the day (and night) a pediatric oncologist in case of problems, in order to discuss necessity for emergency control and/or rehospitalization.

Ages Eligible for Study:  1 Year   -   18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Chemotherapy because of malignancy
• Severe neutropenia (absolute neutrophil count ≤ 0.5x10E9/L)
• Fever (axillary temperature ≥ 38.5°C once or ≥ 38.0°C during ≥ 2 hours)
• Able to swallow oral medication
• Written informed consent from patients and/or parents

Exclusion Criteria:

• Status post myeloablative chemotherapy
• Diagnosis: acute myeloid leukemia, B-cell acute lymphoblastic leukemia, or B-cell Non-Hodgkin lymphoma
• Bone marrow involvement by malignancy ≥ 25%
• Any comorbidity requiring hospitalization: [1] mean arterial blood pressure < 50 mmHg (up to 10 years) / < 60 mmHg (older than 10 years); [2] oxygen saturation < 94% at room air; [3] radiologically defined pneumonia; [4] focal bacterial infection; [5] blood cultures taken at presentation reported positive at reassessment; [6] need for inpatient treatment or observation due to any other reason, as judged by the physician in charge
• Ever shaking chills
• Ever axillary temperature ≥ 39.5°C
• Antibacterial treatment before presentation with fever and neutropenia (except for prevention against Pneumocystis jiroveci [formerly P. carinii] pneumonia)
• Modification or de novo institution of a prophylaxis against P. jiroveci pneumonia
• Modification or de novo institution of a therapy with G-CSF or GM-CSF.
• Allergy to ciprofloxacin and/or amoxicillin
• Serum creatinine level above the upper limit of normal range

Roland A Ammann, MD      0041 31 632 93 72    roland.ammann@insel.ch
Andrea Zaugg, RN      0041 31 632 93 72    spog.2003.fn@insel.ch

Germany
      Pediatric Hematology/Oncology, University Children's Hospital, Bonn,  D-53113,  Germany; Recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Duesseldorf,  D-40225,  Germany; Not yet recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Freiburg,  D-79106,  Germany; Not yet recruiting
      Pediatric Hematology/Oncology, University Children's Hospital von Hauner, Munich,  D-80337,  Germany; Recruiting
Netherlands
      Pediatric Hematology/Oncology, University Children's Hospital, Groningen,  NL-9700,  Netherlands; Not yet recruiting
Switzerland
      Pediatric Hematology/Oncology, University Children's Hospital, Basel,  CH-4005,  Switzerland; Recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Bern,  CH-3010,  Switzerland; Recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Geneva,  CH-1205,  Switzerland; Not yet recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Lausanne,  CH-1011,  Switzerland; Not yet recruiting
      Pediatric Hematology/Oncology, Children's Hospital, Lucerne,  CH-6004,  Switzerland; Not yet recruiting
      Pediatric Hematology/Oncology, Children's Hospital, St. Gallen,  CH-9006,  Switzerland; Not yet recruiting
      Pediatric Hematology/Oncology, University Children's Hospital, Zurich,  CH-8032,  Switzerland; Recruiting

Study chairs or principal investigators

Roland A Ammann, MD,  Study Chair,  Pediatric Hematology/Oncology, University Children's Hospital, Inselspital, CH-3010 Bern, Switzerland   
Christoph Aebi, MD,  Study Director,  University Children's Hospital, Bern, Switzerland   
Maja Beck-Popovic, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Lausanne, Switzerland   
Eveline SJM de Bont, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Groningen, The Netherlands   
Thomas Kuehne, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Basel, Switzerland   
David Nadal, MD,  Study Director,  University Children's Hospital, Zurich, Switzerland   
Felix Niggli, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Zurich, Switzerland   
Annette Ridolfi Luethy, MD,  Study Director,  Pediatric Hematology/Oncology, University Children's Hospital, Bern, Switzerland   
Arne Simon, MD,  Principal Investigator,  Pediatric Hematology/Oncology, University Children's Hospital, Bonn, Germany   

Study ID Numbers:  SPOG 2003 FN; Umbrella Network Trial 2004.3; OCS - 01466-02-2004
Record last reviewed:  April 2005
Last Updated:  April 7, 2005
Record first received:  April 4, 2005
ClinicalTrials.gov Identifier:  NCT00107081
Health Authority: Switzerland: Swissmedic (Awaiting confirmation); Germany: Federal Institute for Drugs and Medicinal Devices (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-08