Anakinra as prevention of fever and mucositis in patients with a stem cell transplantatio

Phase 1

• Conditions: Febrile neutropenia and mucositis; MedDRA version: 20.0Level: LLTClassification code 10028127Term: MucositisSystem Organ Class: 100000004867; MedDRA version: 20.0Level: PTClassification code 10016288Term: Febrile neutropeniaSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-005046-10-NL
• Lead Sponsor: Radboud university medical center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-07-23
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 90

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

- Inability to understand the nature and extent of the trial and the procedures required
- Enrolment 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 TNFa inhibiting agents (such as etanercept, adalimumab, infliximab, certolizumab and golimumab).
- Uncontrolled bacterial or viral infections, or fungal infections, at the start of therapy
- Documented 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 & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the efficacy of anakinra in patients with multiple myeloma receiving high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (SCT). The primary endpoint is the reduction of the incidence of fever during neutropenia.;Secondary Objective: Secondary objectives are the gathering of blood and microbiota samples for translational research.;Primary end point(s): The main study endpoint will be the incidence of fever during neutropenia. This is defined as a tympanic temperature =38.5°C and an absolute neutrophil count (ANC) < 0.5 × 10^9/l, or expected to fall below 0.5 × 10^9/l in the next 48 hours.<br><br><br>;Timepoint(s) of evaluation of this end point: The primary study endpoint will be evaluated at the end of the study (after study treatment of the last patient is completed).