Clinical trial NCT02324231: 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
Official title: SPOG 2015 FN Definition. A Swiss Pediatric Oncology Group (SPOG) Initiated Multi-center Open-label Randomized Controlled Multiple Crossover 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 (FN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Pediatrics
Fever
Neutropenia
Fever in Neutropenia
Lead sponsor: Swiss Pediatric Oncology Group
Sponsor class: OTHER
First posted: 2014-12-24
Enrollment: 269
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of clinically defined FN with at least one safety relevant event
timeFrame: 1 year (estimated average)
Secondary outcomes:
measure: Times and delays of diagnosis and therapy (A)
timeFrame: 1 year (estimated average)
measure: Adverse events (B)
timeFrame: 1 year (estimated average)
measure: Delay from crossing low to high TLDF (C)
timeFrame: 1 year (estimated average)
measure: Rate of clinically defined FN (D)
timeFrame: 1 year (estimated average)
measure: Rate of FN diagnosed at/above TLDF (E)
timeFrame: 1 year (estimated average)
measure: Rate of FN diagnosed below TLDF (E)
timeFrame: 1 year (estimated average)
measure: Duration of treatment (F)
timeFrame: 1 year (estimated average)
measure: Simultaneous and avoided FN diagnoses (G)
timeFrame: 1 year (estimated average)
Other outcomes:
measure: Development of rules predicting risk of FN during chemotherapy
timeFrame: 1 year (estimated average)
measure: Development of rules predicting risk of adverse events during FN
timeFrame: 1 year (estimated average)
measure: External validation of rules predicting risk of FN during chemotherapy
timeFrame: 1 year (estimated average)
measure: External validation of rules predicting risk of adverse events during FN
timeFrame: 1 year (estimated average)
Locations:
city: Basel
country: Switzerland
facility: Basel: Universitätskinderklinik beider Basel
city: Bern
country: Switzerland
facility: Bern: Universitätsklinik für Kinderheilkunde, Inselspital
city: Geneva
country: Switzerland
facility: Geneva: Département de Pédiatrie, Hôpital Cantonal de Genève
city: Lausanne
country: Switzerland
facility: Lausanne: Hémato-Oncologie Pédiatrique, CHUV
city: Lucerne
country: Switzerland
facility: Luzern: Pädiatrische Hämatologie/Onkologie, Kinderspital
city: Zurich
country: Switzerland
facility: Zürich: Pädiatrische Onkologie Kinderspital
Study officials:
affiliation: Universitätsklinik für Kinderheilkunde, Inselspital, Bern
name: Roland A Ammann, MD
role: STUDY_CHAIR
References:
citation: Ammann RA. A sequence of Swiss studies on the temperature Limit defining fever in pediatric oncology. Schweizer Krebsbulletin 35(1): 69-71, 2015.
citation: Lavieri L, Koenig C, Bodmer N, Agyeman PKA, Scheinemann K, Ansari M, Roessler J, Ammann RA. Predicting fever in neutropenia with safety-relevant events in children undergoing chemotherapy for cancer: The prospective multicenter SPOG 2015 FN Definition Study. Pediatr Blood Cancer. 2021 Dec;68(12):e29253. doi: 10.1002/pbc.29253. Epub 2021 Jul 26.
citation: Koenig C, Bodmer N, Agyeman PKA, Niggli F, Adam C, Ansari M, Eisenreich B, Keller N, Leibundgut K, Nadal D, Roessler J, Scheinemann K, Simon A, Teuffel O, von der Weid NX, Zeller M, Zimmermann K, Ammann RA. 39.0 degrees C versus 38.5 degrees C ear temperature as fever limit in children with neutropenia undergoing chemotherapy for cancer: a multicentre, cluster-randomised, multiple-crossover, non-inferiority trial. Lancet Child Adolesc Health. 2020 Jul;4(7):495-502. doi: 10.1016/S2352-4642(20)30092-4. Epub 2020 Jun 1.