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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT04099901
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Radboud University
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Nicole Blijlevens, MD PhDGerwin Huls, MD PhDBart Biemond, MD PhDMartijn Bakker, MD
Principal Investigator Affiliation Radboud UniversityUMCGAmsterdam UMCUMCG
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOther
Overall Status Recruiting
Countries Netherlands
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Multiple Myeloma
Arms & Interventions

Arms

Experimental: Anakinra

Dosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12).

Placebo Comparator: Placebo

Dosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12).

Interventions

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).

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).

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Amsterdam UMC, location AMC, Amsterdam, Netherlands

Status

Not yet recruiting

Address

Amsterdam UMC, location AMC

Amsterdam, ,

Site Contact

Trialbureau Hematologie AMC

hemat.trial@amc.nl

+31-(0)20-5665950

Groningen, Netherlands

Status

Recruiting

Address

University Medical Center Groningen (UMCG)

Groningen, ,

Site Contact

Trialbureau Hematologie UMCG

e.gkoumasi@umcg.nl

+31-(0)50-3615410

Radboudumc, Nijmegen, Netherlands

Status

Recruiting

Address

Radboudumc

Nijmegen, ,

Site Contact

Postbus Trialbureau Hematologie-Oncologie

trialbureauhemat-onco@radboudumc.nl

+31243614794