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

NCT ID: NCT04099901

Last Updated: 2024-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 88 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-11-04
• Study Completion Date: 2024-02-26

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Anakinra

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

Group Type: EXPERIMENTAL

Anakinra

Intervention Type: 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).

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: 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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Kineret

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Dutch Cancer Society

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicole Blijlevens, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Gerwin Huls, MD PhD

Role: PRINCIPAL_INVESTIGATOR

UMCG

Bart Biemond, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Martijn Bakker, MD

Role: PRINCIPAL_INVESTIGATOR

UMCG

Locations

Amsterdam UMC, location AMC

Amsterdam, , Netherlands

University Medical Center Groningen (UMCG)

Groningen, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 33225965 (View on PubMed)

Other Identifiers

HEMSC42

Identifier Type: -

Identifier Source: org_study_id