Multiple MyelomaPhase 2AFFECT-2NCT04099901
Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT - A Randomized Controlled Trial
A Phase 2 study testing Anakinra in people with Multiple Myeloma, run by Radboud University Medical Center at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Anakinra
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 3 sitesNetherlands
- Study dates
- 4 Nov 2019to 26 Feb 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Amsterdam UMC, location AMC
Amsterdam
University Medical Center Groningen (UMCG)
Groningen
Radboudumc
Nijmegen
About this study
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
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.
Read more
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
- Being tested
- Anakinra, Placebos
- Keywords
- Anakinra, Mucositis, Hematopoietic stem cell transplantation, Febrile neutropenia
- Medical subject headings
- Multiple Myeloma, Mucositis, Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnakinraDrug
Also called Kineret
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).
PlacebosDrug
Subjects will be treated with a daily dose of placebo, intravenously, starting on day -2, until day +12 (day 0 is day of SCT).
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | Dosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12). Receives: Drug: Anakinra |
| Placebo | Placebo comparator | Dosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12). Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction of the incidence of fever during neutropenia
Measured: Primary outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Secondary outcomes (14)
Reduction in incidence of mucositis-related fever
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Daily mean CRP level
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Clinical mucositis as determined by the daily mouth and gut scores
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Days with fever (≥ 38.5° C)
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Incidence of bloodstream infections i.e. bacteremia
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Length of hospital stay in days
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of systemic antimicrobial agents (incidence and duration)
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of analgesic drugs (incidence and duration)
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Use of total parenteral nutrition (TPN) (incidence and duration)
Measured: Outcome will be determined during the period of hospitalization (day of admission [day -3] until discharge, maximum period +30 days).
Quality of life according to the EORTC QLQ-C30
Quality of life according to the EORTC QLQ-C30
Measured: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Fatigue severity according to the FACIT-Fatigue scale
Severity of fatigue as the score measured by the validated FACIT-Fatigue scale
Measured: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Short term overall survival
Measured: +100 days and +1 year
Tumor response evaluation
Measured: +100 days and +1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2019
- Study start4 Nov 2019
- Primary completion14 Mar 2023
- Study completion26 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind placebo-controlled randomized trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen, Dutch Cancer Society
- Responsible party
- Sponsor
- Investigators
- Nicole Blijlevens, MD PhD, Principal investigator, Radboud University Medical CenterGerwin Huls, MD PhD, Principal investigator, University Medical Center GroningenBart Biemond, MD PhD, Principal investigator, Amsterdam UMCMartijn Bakker, MD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04099901
- Sponsor's protocol ID
- HEMSC42
- Acronym
- AFFECT-2
- Status last verified
- Nov 2023
- First submitted
- 18 Sep 2019
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 33225965
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04099901
- Acronym / sponsor ID
- AFFECT-2 / HEMSC42
- Conditions
- Multiple Myeloma
- Keywords
- Anakinra, Mucositis, Hematopoietic stem cell transplantation, Febrile neutropenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- University Medical Center Groningen, Dutch Cancer Society
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 14 Mar 2023 (actual)
- Study completion
- 26 Feb 2024 (actual)
- First posted
- 23 Sep 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blind placebo-controlled randomized trial
| Arm | Type | Receives |
|---|---|---|
| Anakinra | Experimental | Drug: AnakinraDosage form: intravenous. Dosage: 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12). |
| Placebo | Placebo comparator | Drug: PlacebosDosage form: intravenous. Dosage: not applicable. Frequency: once daily. Duration: 15 days (day -2 until day +12). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnakinraAlso: KineretSubjects 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). | Drug | Anakinra |
| PlacebosSubjects will be treated with a daily dose of placebo, intravenously, starting on day -2, until day +12 (day 0 is day of SCT). | Drug | Placebo |
Primary outcome
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).
14 secondary outcomes
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Quality of life according to the EORTC QLQ-C30
Time frame: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Fatigue severity according to the FACIT-Fatigue scale
Time frame: Baseline, +30 days/discharge (whichever comes first), +100 days, +1 year
Short term overall survival
Time frame: +100 days and +1 year
Tumor response evaluation
Time frame: +100 days and +1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2024.
- Derived from this study: PubMed 33225965de 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.
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicole Blijlevens, MD PhD principal investigator
Radboud University Medical Center
Gerwin Huls, MD PhD principal investigator
University Medical Center Groningen
Bart Biemond, MD PhD principal investigator
Amsterdam UMC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra in people with Multiple Myeloma, run by Radboud University Medical Center at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04099901, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2024.