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

NCT04099901 | Completed Phase 2 DMC

• 1 other identifier: HEMSC42
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Anakinra; Mucositis; Hematopoietic stem cell transplantation; Febrile neutropenia

Outcome Measures

Primary Outcomes (1)

• Reduction of the incidence of fever during neutropenia

  Primary outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).

Secondary Outcomes (14)

• Reduction in incidence of mucositis-related fever

  Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).

• Daily mean CRP level

  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

  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

  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)

  Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).

Study Arms (2)

Anakinra

EXPERIMENTAL

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

Drug: Anakinra

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Anakinra DRUG

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).

Also known as: Kineret

Anakinra

Placebos DRUG

Subjects will be treated with a daily dose of placebo, intravenously, starting on day -2, until day +12 (day 0 is day of SCT).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• University Medical Center Groningen: collaborator
• Dutch Cancer Society: collaborator

Study Sites (3)

Amsterdam UMC, location AMC

Amsterdam, Netherlands

Location

University Medical Center Groningen (UMCG)

Groningen, Netherlands

Location

Radboudumc

Nijmegen, Netherlands

Location

Related Publications (1)

• de Mooij CEM, van Groningen LFJ, de Haan AFJ, Biemond BJ, Bakker M, van der Velden WJFM, Blijlevens NMA. 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. Trials. 2020 Nov 23;21(1):948. doi: 10.1186/s13063-020-04847-5.

  PMID: 33225965 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Mucositis; Febrile Neutropenia

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Mouth Diseases; Stomatognathic Diseases; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Nicole Blijlevens, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Gerwin Huls, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

• Bart Biemond, MD PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

• Martijn Bakker, MD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blind placebo-controlled randomized trial

Study Record Dates

• First Submitted: September 18, 2019
• First Posted: September 23, 2019
• Study Start: November 4, 2019
• Primary Completion: March 14, 2023
• Study Completion: February 26, 2024
• Last Updated: November 18, 2024

Record last verified: 2023-11

Locations

NL (3)