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

Radboud University Medical Center

Status and phase

Completed

Phase 2

Conditions

Multiple Myeloma

Treatments

Drug: Anakinra

Drug: Placebos

Study type

Interventional

Funder types

Other

Identifiers

NCT04099901

HEMSC42

Details and patient eligibility

About

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.

Enrollment

88 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.