Multiple MyelomaPhase 2AFFECT-1NCT03233776
Anakinra: Safety and Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT
A Phase 2 study testing Anakinra in people with Multiple Myeloma, run by Radboud University Medical Center at 1 site 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?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteNetherlands
- Study dates
- 21 Aug 2017to 2 Apr 2020
- 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
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- 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.
Who cannot join
- 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
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- 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
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Efficacy of Interleukin-1 Inhibitor Anakinra for the Amelioration of Fever During Neutropenia and Mucositis in Patients With Multiple Myeloma Receiving an Autologous Stem Cell Transplantation After High-dose Melphalan
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 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.
In this phase IIa study the safety, maximum tolerated dose and efficacy of anakinra, a recombinant human IL-1 receptor antagonist, will be determined in adult patients with multiple myeloma who receive high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (ASCT) and are at high risk for experiencing mucositis and fever during neutropenia (FN). After establishing the optimal dose, a pivotal double-blind randomized placebo-controlled multicenter phase IIb trial will be planned to establish efficacy.
- Conditions
- Multiple Myeloma
- Being tested
- Anakinra
- 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 anakinra, intravenously, starting on day -2, until day +12 (day 0 is day of SCT). Predefined doses are 100 mg , 200 mg and 300 mg.
| Study group | Role | What they receive |
|---|---|---|
| Anakinra | Experimental | Dosage form: intravenous. Dosage: either 100 mg, 200 mg or 300 mg. Frequency: once daily. Duration: 15 days (day -2 until day +12). Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Establish the maximum tolerated dose of anakinra (MTD, 100, 200 or 300 mg).
In this study, using a traditional 3+3 design, 3 doses of anakinra will be examined: 100, 200 and 300 mg. The first cohort of patients will start with 100 mg. Escalation to the next dose cohort(s) is based on the occurrence of dose limiting toxicities (DLTs). The definition of a DLT is: an opportunistic infection, a SUSAR, severe non-hematological toxicity grade 3-4, or the occurrence of primary graft failure or prolonged neutropenia (neutrophils have not been >0.5 x10^9/l on one single day, assessed on day +21, and counting from day 0).
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Secondary outcomes (14)
Incidence of fever during neutropenia
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Incidence of mucositis-related fever
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Daily mean CRP level
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Clinical mucositis as determined by the daily mouth and gut scores
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Days with fever (≥ 38.5° C)
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Incidence of bloodstream infections i.e. bacteremia
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Length of hospital stay in days
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of systemic antimicrobial agents (incidence and duration)
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of analgesic drugs (incidence and duration)
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of total parenteral nutrition (TPN) (incidence and duration)
Measured: Day of admission (day -2) until discharge. Maximum period: +30 days.
Quality of life
Quality of life according to the EORTC QLQ-C30
Measured: Baseline, at discharge (average: 23 days; maximum: after 30 days), +100 days, +1 year
Fatigue severity
Severity of fatigue as the score measured by the validated FACIT-Fatigue scale
Measured: Baseline, at discharge (average: 23 days; maximum: after 30 days), +100 days, +1 year
Short term overall survival
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 posted31 Jul 2017
- Study start21 Aug 2017
- Primary completion2 Apr 2020
- Study completion2 Apr 2020
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
- Not applicable
- Intervention model
- Sequential
- Model description
- 3+3 design
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicole Blijlevens, MD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03233776
- Sponsor's protocol ID
- SC35
- Acronym
- AFFECT-1
- Status last verified
- Nov 2020
- First submitted
- 19 Jul 2017
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wardill HR, de Mooij CEM, Da Silva Ferreira AR, Havinga H, Harmsen HJM, van der Velden WJFM, van Groningen LFJ, Tissing WJE, Blijlevens NMA. Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra. Sci Rep. 2022 May 11;12(1):6803. doi: 10.1038/s41598-022-10700-3.
PubMed 35546555
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
- Safety and Efficacy of Interleukin-1 Inhibitor Anakinra for the Amelioration of Fever During Neutropenia and Mucositis in Patients With Multiple Myeloma Receiving an Autologous Stem Cell Transplantation After High-dose Melphalan
- ClinicalTrials.gov ID
- NCT03233776
- Acronym / sponsor ID
- AFFECT-1 / SC35
- Conditions
- Multiple Myeloma
- Keywords
- Anakinra, Mucositis, Hematopoietic stem cell transplantation, Febrile neutropenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 21 Aug 2017 (actual)
- Primary completion
- 2 Apr 2020 (actual)
- Study completion
- 2 Apr 2020 (actual)
- First posted
- 31 Jul 2017 (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 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.
In this phase IIa study the safety, maximum tolerated dose and efficacy of anakinra, a recombinant human IL-1 receptor antagonist, will be determined in adult patients with multiple myeloma who receive high-dose melphalan (HDM) in the preparation for an autologous hematopoietic stem cell transplantation (ASCT) and are at high risk for experiencing mucositis and fever during neutropenia (FN). After establishing the optimal dose, a pivotal double-blind randomized placebo-controlled multicenter phase IIb trial will be planned to establish efficacy.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3+3 design
| Arm | Type | Receives |
|---|---|---|
| Anakinra | Experimental | Drug: AnakinraDosage form: intravenous. Dosage: either 100 mg, 200 mg or 300 mg. 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 (11 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
- 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.
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 anakinra, intravenously, starting on day -2, until day +12 (day 0 is day of SCT). Predefined doses are 100 mg , 200 mg and 300 mg. | Drug | Anakinra |
Primary outcome
Establish the maximum tolerated dose of anakinra (MTD, 100, 200 or 300 mg).
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
In this study, using a traditional 3+3 design, 3 doses of anakinra will be examined: 100, 200 and 300 mg. The first cohort of patients will start with 100 mg. Escalation to the next dose cohort(s) is based on the occurrence of dose limiting toxicities (DLTs). The definition of a DLT is: an opportunistic infection, a SUSAR, severe non-hematological toxicity grade 3-4, or the occurrence of primary graft failure or prolonged neutropenia (neutrophils have not been >0.5 x10^9/l on one single day, assessed on day +21, and counting from day 0).
14 secondary outcomes
Incidence of fever during neutropenia
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Incidence of mucositis-related fever
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Daily mean CRP level
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Intestinal mucositis as measured by the area-under-the-curve of reciprocal citrulline levels
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Clinical mucositis as determined by the daily mouth and gut scores
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Days with fever (≥ 38.5° C)
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Incidence of bloodstream infections i.e. bacteremia
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Length of hospital stay in days
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of systemic antimicrobial agents (incidence and duration)
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of analgesic drugs (incidence and duration)
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Use of total parenteral nutrition (TPN) (incidence and duration)
Time frame: Day of admission (day -2) until discharge. Maximum period: +30 days.
Quality of life
Time frame: Baseline, at discharge (average: 23 days; maximum: after 30 days), +100 days, +1 year
Fatigue severity
Time frame: Baseline, at discharge (average: 23 days; maximum: after 30 days), +100 days, +1 year
Short term overall survival
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 35546555Wardill HR, de Mooij CEM, Da Silva Ferreira AR, Havinga H, Harmsen HJM, van der Velden WJFM, van Groningen LFJ, Tissing WJE, Blijlevens NMA. Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with anakinra. Sci Rep. 2022 May 11;12(1):6803. doi: 10.1038/s41598-022-10700-3.
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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
1 site 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 1 site 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 11 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 1 site 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. 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?
Establish the maximum tolerated dose of anakinra (MTD, 100, 200 or 300 mg). (time frame: Day of admission (day -2) 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 NCT03233776, 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.