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

NCT02324231 | Completed DMC

• 1 other identifier: SPOG 2015 FN Definition
• Study Type: interventional
• Target: 269
• Locations: 1 country
• Sites: 6

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.

Conditions

Cancer; Pediatrics; Fever; Neutropenia; Fever in Neutropenia

Outcome Measures

Primary Outcomes (1)

• 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)

  1 year (estimated average)

Secondary Outcomes (8)

• Times and delays of diagnosis and therapy (A)

  1 year (estimated average)

• Adverse events (B)

  1 year (estimated average)

• Delay from crossing low to high TLDF (C)

  1 year (estimated average)

• Rate of clinically defined FN (D)

  1 year (estimated average)

• Rate of FN diagnosed at/above TLDF (E)

  1 year (estimated average)

Other Outcomes (4)

• Development of rules predicting risk of FN during chemotherapy

  1 year (estimated average)

• Development of rules predicting risk of adverse events during FN

  1 year (estimated average)

• External validation of rules predicting risk of FN during chemotherapy

  1 year (estimated average)

Study Arms (2)

39.0°C temperature limit defining fever

OTHER

Temperature limit defining fever, for definition of fever in neutropenia (FN), is single temperature \>=39.0°C measured in the ear by infrared tympanic thermometry. If clinically indicated, the treating physician is allowed to make the diagnosis of FN at lower temperatures.

Other: 39.0°C temperature limit defining fever

38.5°C temperature limit defining fever

OTHER

Temperature limit defining fever, for definition of fever in neutropenia (FN), is single temperature \>=38.5°C measured in the ear by infrared tympanic thermometry. If clinically indicated, the treating physician is allowed to make the diagnosis of FN at lower temperatures.

Other: 38.5°C temperature limit defining fever

Interventions

39.0°C temperature limit defining fever OTHER

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

39.0°C temperature limit defining fever

38.5°C temperature limit defining fever OTHER

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 fever

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Swiss Pediatric Oncology Group: lead

Study Sites (6)

Basel: Universitätskinderklinik beider Basel

Basel, CH-4031, Switzerland

Location

Bern: Universitätsklinik für Kinderheilkunde, Inselspital

Bern, CH-3010, Switzerland

Location

Geneva: Département de Pédiatrie, Hôpital Cantonal de Genève

Geneva, CH-1211, Switzerland

Location

Lausanne: Hémato-Oncologie Pédiatrique, CHUV

Lausanne, CH-1011, Switzerland

Location

Luzern: Pädiatrische Hämatologie/Onkologie, Kinderspital

Lucerne, CH-6000, Switzerland

Location

Zürich: Pädiatrische Onkologie Kinderspital

Zurich, CH-8032, Switzerland

Location

Related Publications (3)

• Ammann RA. A sequence of Swiss studies on the temperature Limit defining fever in pediatric oncology. Schweizer Krebsbulletin 35(1): 69-71, 2015.

  BACKGROUND

• 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.

  PMID: 34310027 DERIVED

• 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.

  PMID: 32497520 DERIVED

MeSH Terms

Conditions

Neoplasms; Fever; Neutropenia

Condition Hierarchy (Ancestors)

Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Study Officials

• Roland A Ammann, MD

  Universitätsklinik für Kinderheilkunde, Inselspital, Bern

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2014
• First Posted: December 24, 2014
• Study Start: April 1, 2016
• Primary Completion: September 15, 2018
• Study Completion: September 15, 2018
• Last Updated: February 21, 2019

Record last verified: 2018-10

Locations

CH (6)