SPOG 2015 FN Definition. A Multi-center Non-inferiority Trial on Safety of a High Versus Low Temperature Limit Defining Fever in Pediatric Patients With Cancer at Risk for Fever in Chemotherapy-induced Neutropenia

Swiss Pediatric Oncology Group269 enrolled

Overview

In a multi-center open-label cluster-randomized controlled parallel-group multiple crossover non-inferiority trial in children and adolescents up to 20 years diagnosed with cancer requiring chemotherapy, primarily the safety, and secondarily the efficacy and other endpoints, of a high (39.0°C) versus low (38.5°C) temperature limit defining fever (TLDF) for the diagnosis of fever in chemotherapy-induced neutropenia (FN) is studied. Safety is assessed by the rate of safety relevant events per chemotherapy exposure time, a composite endpoint including serious medical complications and bacteremia during FN. Patients are repeatedly randomized (cluster: study site) to the high or the low TLDF every month, resulting in possible multiple crossovers in one patient. The high TLDF is declared not to be inferior regarding safety compared to the low TLDF if non-inferiority of the rate ratio of safety relevant events is proven, with a single-sided non-inferiority margin of 1.33, applying mixed Poisson regression.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

NONE

Enrollment

269

Conditions

Cancer Pediatrics Fever

Interventions

39.0°C temperature limit defining feverOTHER

Diagnosis of FN, correspondingly hospitalization and start of empirical intravenous broad-spectrum antimicrobial therapy. Further treatment according to treating physician.

38.5°C temperature limit defining feverOTHER

Diagnosis of FN, correspondingly hospitalization and start of empirical intravenous broad-spectrum antimicrobial therapy. Further treatment according to treating physician.

Eligibility

Sex: ALLMin age: 1 YearMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Chemotherapy treatment because of any malignancy for at least 2 months at time of recruitment for myelosuppressive therapy, or at least 1 cycle of myeloablative chemotherapy followed by autologous hematopoietic stem cell transplantation * Age ≥12 months and \<18 years at time of recruitment * Written informed consent from patients and/or parents Exclusion Criteria: * Infants \<1 years old (reason: differences in temperature measurement method) * Past allogeneic hematopoietic stem cell transplantation * Denied written informed consent from patients and/or parents

Locations (6)

Basel: Universitätskinderklinik beider Basel

Basel, Switzerland

Bern: Universitätsklinik für Kinderheilkunde, Inselspital

Bern, Switzerland

Geneva: Département de Pédiatrie, Hôpital Cantonal de Genève

Geneva, Switzerland

Lausanne: Hémato-Oncologie Pédiatrique, CHUV

Lausanne, Switzerland

Luzern: Pädiatrische Hämatologie/Onkologie, Kinderspital

Lucerne, Switzerland

Zürich: Pädiatrische Onkologie Kinderspital

Zurich, Switzerland

Outcomes

Primary Outcomes

Rate of clinically defined FN with at least one safety relevant event

Poisson rate: number of clinically defined FN with at least one SRE divided by the entire chemotherapy exposure time for each patient, estimated to be 1 year on average (Unit: FN per year of chemotherapy exposure time) SRE: Composite endpoint (serious medical complication AND/OR bacteremia), reached until the end of each individual FN episode (Unit: binary)