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Published in: Trials 1/2020

01-12-2020 | Multiple Myeloma | Study protocol

Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)—study protocol for a multicenter randomized double-blind placebo-controlled trial

Authors: Charlotte E. M. de Mooij, Lenneke F. J. van Groningen, Anton F. J. de Haan, Bart J. Biemond, Martijn Bakker, Walter J. F. M. van der Velden, Nicole M. A. Blijlevens

Published in: Trials | Issue 1/2020

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Abstract

Background

Since decades, fever and infections have been the most important complications of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT) in the treatment of hematologic malignancies. Neutropenia has long been considered to be the most important risk factor for these complications. However, recent studies have shown that not neutropenia, but the development of mucositis is the most important cause of these complications. Currently, limited options for the prevention and treatment of mucositis are available, of which most are only supportive. The pro-inflammatory cytokine interleukin-1 (IL-1) plays a crucial role in the pathogenesis of mucositis. Pre-clinical studies of chemotherapy-induced mucositis have shown that recombinant human IL-1 receptor antagonist anakinra significantly ameliorated intestinal mucositis. In our pilot study AFFECT-1, we examined the safety and maximal tolerated dose of anakinra in patients with multiple myeloma, treated with high-dose melphalan (HDM) and autologous HSCT, selecting a dose of 300 mg daily for the phase IIb trial. The aim of the AFFECT-2 study is to determine the efficacy of anakinra in preventing fever during neutropenia (FN) and mucositis in this study population.

Methods/design

A multicenter, randomized, placebo-controlled, double-blind phase IIb trial will be conducted. Ninety patients with multiple myeloma scheduled for treatment with HDM and autologous HSCT will be included. Patients will be randomized between intravenous treatment with anakinra (300 mg) or placebo. Each group will be treated from day − 2 (day of HDM; day 0 is HSCT) up until day + 12. Outcome measures will be assessed at baseline, during admission, at discharge or day + 30, at day + 90, and + 1 year. The primary outcome will be reduction of FN. Secondary outcome measures include mucositis scores, bloodstream infections, citrulline levels, quality of life, and fatigue severity.

Discussion

The AFFECT-2 trial will examine the efficacy of anakinra in the management of fever during neutropenia and mucositis in patients with multiple myeloma treated with HDM and autologous HSCT. The results of this study may provide a new treatment option for these important complications. Also, this study will give us more insight in the pathophysiology of mucositis, including the role of IL-1 and the role of the microbiota in mucositis.

Trial registration

Clinicaltrials.gov NCT04099901. Registered on September 23, 2019. EudraCT: 2018-005046-10.
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Metadata
Title
Anakinra: efficacy in the management of fever during neutropenia and mucositis in autologous stem cell transplantation (AFFECT-2)—study protocol for a multicenter randomized double-blind placebo-controlled trial
Authors
Charlotte E. M. de Mooij
Lenneke F. J. van Groningen
Anton F. J. de Haan
Bart J. Biemond
Martijn Bakker
Walter J. F. M. van der Velden
Nicole M. A. Blijlevens
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Trials / Issue 1/2020
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-020-04847-5

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