Back to resultsAnakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT - A Randomized Controlled Trial (AFFECT-2)
Primary Purpose
Multiple Myeloma
Status
Active
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Anakinra
Placebos
Sponsored by
About this trial
This is an interventional supportive care trial for Multiple Myeloma focused on measuring Anakinra, Mucositis, Hematopoietic stem cell transplantation, Febrile neutropenia
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.
Sites / Locations
- Amsterdam UMC, location AMC
- University Medical Center Groningen (UMCG)
- Radboudumc
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Anakinra
Placebo
Arm Description
Dosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Dosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Outcomes
Primary Outcome Measures
Reduction of the incidence of fever during neutropenia
Secondary Outcome Measures
Reduction in incidence of mucositis-related fever
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 (≥ 38.5° C)
Incidence of bloodstream infections i.e. bacteremia
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)
Quality of life according to the EORTC QLQ-C30
Quality of life according to the EORTC QLQ-C30
Fatigue severity according to the FACIT-Fatigue scale
Severity of fatigue as the score measured by the validated FACIT-Fatigue scale
Short term overall survival
Tumor response evaluation
Full Information
NCT ID
NCT04099901
First Posted
September 18, 2019
Last Updated
March 29, 2023
Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT04099901
Brief Title
Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT - A Randomized Controlled Trial
Acronym
AFFECT-2
Official Title
Anakinra: Efficacy of Anakinra for the Management of Fever During Neutropenia and Mucositis in Patients With Multiple Myeloma Receiving an Autologous Hematopoietic Stem Cell Transplantation After High-dose Melphalan - An RCT
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 4, 2019 (Actual)
Primary Completion Date
March 14, 2023 (Actual)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Anakinra, Mucositis, Hematopoietic stem cell transplantation, Febrile neutropenia
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blind placebo-controlled randomized trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
88 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Anakinra
Arm Type
Experimental
Arm Description
Dosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Dosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12).
Intervention Type
Drug
Intervention Name(s)
Anakinra
Other Intervention Name(s)
Kineret
Intervention Description
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
Intervention Name(s)
Placebos
Intervention Description
Subjects will be treated with a daily dose of placebo, intravenously, starting on day -2, until day +12 (day 0 is day of SCT).
Primary Outcome Measure Information:
Title
Reduction of the incidence of fever during neutropenia
Time Frame
Primary outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Secondary Outcome Measure Information:
Title
Reduction in incidence of mucositis-related fever
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Daily mean CRP level
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Clinical mucositis as determined by the daily mouth and gut scores
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Days with fever (≥ 38.5° C)
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Incidence of bloodstream infections i.e. bacteremia
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Length of hospital stay in days
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Use of systemic antimicrobial agents (incidence and duration)
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Use of analgesic drugs (incidence and duration)
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Use of total parenteral nutrition (TPN) (incidence and duration)
Time Frame
Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Title
Quality of life according to the EORTC QLQ-C30
Description
Quality of life according to the EORTC QLQ-C30
Time Frame
Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Title
Fatigue severity according to the FACIT-Fatigue scale
Description
Severity of fatigue as the score measured by the validated FACIT-Fatigue scale
Time Frame
Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Title
Short term overall survival
Time Frame
+100 days and +1 year
Title
Tumor response evaluation
Time Frame
+100 days and +1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicole Blijlevens, MD PhD
Organizational Affiliation
Radboud University Medical Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gerwin Huls, MD PhD
Organizational Affiliation
UMCG
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Bart Biemond, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Martijn Bakker, MD
Organizational Affiliation
UMCG
Official's Role
Principal Investigator
Facility Information:
Facility Name
Amsterdam UMC, location AMC
City
Amsterdam
Country
Netherlands
Facility Name
University Medical Center Groningen (UMCG)
City
Groningen
Country
Netherlands
Facility Name
Radboudumc
City
Nijmegen
Country
Netherlands
12. IPD Sharing Statement
Citations:
PubMed Identifier
33225965
Citation
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.
Results Reference
derived
Learn more about this trial
Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT - A Randomized Controlled Trial
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