Mucositis and febrile neutropenia MedDRA version: 19.0 Level: LLT Classification code 10028127 Term: Mucositis System Organ Class: 100000004867 MedDRA version: 19.0 Level: PT Classification code 10016288 Term: Febrile neutropenia System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Kineret
Pharmaceutical Form: Injection
INN or Proposed INN: ANAKINRA
CAS Number: 143090-92-0
Current Sponsor code: ANAKINRA
Other descriptive name: ANAKINRA
Concentration unit: mg/ml milli
Sponsors
Radboud university medical center
Eligibility
Sex/Gender
All
Inclusion 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 a negative tuberculosis Quantiferon test - 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 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 18
Exclusion criteria
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 inhibitor, such as anakinra, rilonacept or canakinumab, within three months prior to baseline visit - Treatment with TNF 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 highly resistant microorganisms (HRMOs, in Dutch: BRMO’s), prior to registration, or detected during screening procedures - Documented colonization with methicillin-resistant Staphylococcus aureus (MRSA), prior to registration - Subjects who are not able to receive antibacterial prophylaxis with quinolones (because of hypersensitivity) - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: DLTs will be evaluated during and after treatment of every subject. Overall safety and maximum tolerated dose will be evaluated at the end of the study.;Main Objective: The primary objective is to evaluate the safety and efficacy of anakinra in patients with multiple myeloma receiving high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (SCT). ;Secondary Objective: Secondary objectives are the gathering of blood and microbiota samples for translational research.;Primary end point(s): Establish the safety of anakinra as well as the maximum tolerated dose (MTD). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Incidence of fever during neutropenia - Incidence of mucositis-related fever - Maximum CRP level on day +9-10 - Daily mean CRP level - Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels - Clinical mucositis as determined by the daily mouth and gut scores - Days with fever ((= 38.2° C) - Days with fever (= 38.5° C) - Mean daily morning temperature - Area under the curve of daily morning temperature - Incidence of bloodstream infections i.e. bacteremia - Type of bloodstream infections - Incidence of persistently positive blood cultures on day +4 - Quality of life according to the EORTC QLQ-C30 - Severity of fatigue as the score measured by the validated FACIT-Fatigue scale - Short term overall survival (100 days and 1 year) - Length of hospital stay in days - Use of systemic antimicrobial agents (incidence and duration) - Use of analgesic drugs (incidence and duration) - Use of total parenteral nutrition (TPN) (incidence and duration) ;Timepoint(s) of evaluation of this end point: Safety-related endpoints will be evaluated after treatment is completed. Other endpoints will be evaluated after all subjects have finished that part of the study. | — |
Countries
Netherlands
Contacts
Public ContactTrialbureau Hematologie-Oncologie
Radboud university medical center
Outcome results
None listed