Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT - A Randomized Controlled Trial (AFFECT-2)

November 14, 2024 updated by: Radboud University Medical Center

Anakinra: Efficacy of Anakinra for the Management of Fever During Neutropenia and Mucositis in Patients With Multiple Myeloma Receiving an Autologous Hematopoietic Stem Cell Transplantation After High-dose Melphalan - An RCT

Oral and intestinal mucositis are major risk factors for the occurrence of fever during neutropenia and bloodstream infections after intensive chemo- and radiotherapy. These complications often require dose reductions or cause delay of treatment, and thereby interfere with optimal anticancer treatment. Currently, there are no effective strategies to prevent or treat mucositis and the related complications.

The pro-inflammatory cytokine interleukin-1β (IL-1β) has shown to be pivotal in the pathogenesis of mucositis and recently, it has been established in murine models that IL-1 inhibition significantly ameliorates chemotherapy-induced intestinal mucositis.

The investigators recently conducted a phase IIa study (AFFECT-1, NCT03233776) studying the safety and maximum tolerated dose of anakinra, a recombinant human IL-1 receptor antagonist in adult patients with multiple myeloma receiving high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (ASCT) who are at high risk for experiencing mucositis and fever during neutropenia (FN).

Since treatment with anakinra has shown to be safe in this study population, the investigators will continue with a double-blind randomized placebo-controlled multicenter phase IIb trial to establish efficacy in the management of fever during neutropenia and mucositis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Amsterdam UMC, location AMC
      • Groningen, Netherlands
        • University Medical Center Groningen (UMCG)
      • Nijmegen, Netherlands
        • Radboudumc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Aged ≥ 18 years
  • Diagnosed with multiple myeloma
  • Scheduled to receive an autologous SCT after myeloablative therapy with high-dose melphalan
  • Managed with a central venous catheter (triple- or quadruple lumen)
  • Is able and willing to participate
  • Has provided written informed consent
  • Has negative serology for active hepatitis B and C
  • Has negative serology for HIV
  • Has no known hypersensitivity to Escherichia coli derived products or any components of anakinra
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation (during treatment with study medication), and for 30 days after the last dose.

Exclusion Criteria:

  • Inability to understand the nature and extent of the trial and the procedures required
  • Enrollment in any other investigational treatment study or use of an investigational agent during the stem cell transplantation (this means studies in multiple myeloma regarding induction or maintenance treatment are permitted).
  • Women who are pregnant or nursing
  • Diagnosed with amyloidosis or light-chain deposition disease
  • ALT or AST greater than 2.0 x upper limit of normal (ULN) of the local laboratories values.
  • Bilirubin levels greater than 2.0 x upper limit of normal (ULN) of the local laboratories values, except for benign non-malignant indirect hyperbilirubinemia such as Gilbert syndrome
  • Impaired renal function with eGFR <40 ml/min
  • Received a live vaccine during the 3 months prior to baseline visit
  • Recent use of IL-1 antagonist, such as anakinra, rilonacept or canakinumab, within three months prior to baseline visit
  • Treatment with TNFα inhibiting agents (such as etanercept, adalimumab, infliximab, certolizumab and golimumab).
  • Uncontrolled bacterial or viral infections, or fungal infections, at the start of therapy
  • Colonization with methicillin-resistant Staphylococcus aureus (MRSA), carbapenemase-producing Enterobacteriaceae (CPE) or vancomycin-resistant enterococci (VRE) prior to registration
  • Gram-negative colonization resistant to prophylaxis with ciprofloxacin or colistin/cotrimoxazole
  • Subjects who are not able to receive antibacterial prophylaxis with ciprofloxacin or colistin/cotrimoxazole (because of hypersensitivity or drug interactions)
  • Subjects with an active solid malignancy prior to registration, with the exception of cutaneous basal or squamous cell carcinomas
  • History of mycobacterial infection.
  • Subjects with intrinsic disorders of the gastro-intestinal (GI) tract, including, but not limited to: Crohn's disease, ulcerative colitis, celiac disease, short bowel syndrome.
  • Subject has any concurrent medical or psychiatric condition or disease that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra
Dosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Drug: Anakinra
Subjects will be treated with a daily dose of 300 mg anakinra, intravenously, starting on day -2, until day +12 (day 0 is day of SCT).
Other Names:
  • Kineret
Placebo Comparator: Placebo
Dosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Drug: Placebos
Subjects will be treated with a daily dose of placebo, intravenously, starting on day -2, until day +12 (day 0 is day of SCT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction of the incidence of fever during neutropenia
Time Frame: Primary outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Primary outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reduction in incidence of mucositis-related fever
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Daily mean CRP level
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Clinical mucositis as determined by the daily mouth and gut scores
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Days with fever (≥ 38.5° C)
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Incidence of bloodstream infections i.e. bacteremia
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Length of hospital stay in days
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of systemic antimicrobial agents (incidence and duration)
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of analgesic drugs (incidence and duration)
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of total parenteral nutrition (TPN) (incidence and duration)
Time Frame: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Quality of life according to the EORTC QLQ-C30
Time Frame: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Quality of life according to the EORTC QLQ-C30
Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Fatigue severity according to the FACIT-Fatigue scale
Time Frame: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Severity of fatigue as the score measured by the validated FACIT-Fatigue scale
Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Short term overall survival
Time Frame: +100 days and +1 year
+100 days and +1 year
Tumor response evaluation
Time Frame: +100 days and +1 year
+100 days and +1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

University Medical Center Groningen
Dutch Cancer Society

Investigators

  • Principal Investigator: Nicole Blijlevens, MD PhD, Radboud University Medical Center
  • Principal Investigator: Gerwin Huls, MD PhD, UMCG
  • Principal Investigator: Martijn Bakker, MD, UMCG
  • Principal Investigator: Bart Biemond, MD PhD, Amsterdam UMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 4, 2019

Primary Completion (Actual)

March 14, 2023

Study Completion (Actual)

February 26, 2024

Study Registration Dates

First Submitted

September 18, 2019

First Submitted That Met QC Criteria

September 20, 2019

First Posted (Actual)

September 23, 2019

Study Record Updates

Last Update Posted (Estimated)

November 18, 2024

Last Update Submitted That Met QC Criteria

November 14, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HEMSC42

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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