InfluenzaPhase 2SHIVERING 2NCT02566265
Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients
A Phase 2 study testing Fluzone High Dose Vaccine in people with Influenza and Multiple Myeloma, run by Yale University at 1 site in United States.
Trial summary
The investigators' hypothesis is that the administration of Fluzone® High-Dose with booster to all patients with monoclonal gammopathies (irrespective of age) will lead to seroconversion rates exceeding 50% and more importantly, will reduce influenza-related morbidity, reduce interruptions in cancer therapy and may… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Influenza, Multiple Myeloma, Waldenstrom's Macroglobulinemia
- What is being tested?
- Fluzone High Dose Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2015to Jun 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Understand and voluntarily sign an informed consent form.
- Age ≥18 years at the time of signing the informed consent form.
- Diagnosis of any monoclonal gammopathy: Monoclonal Gammopathy of Undetermined Significance (MGUS), asymptomatic / active multiple myeloma, asymptomatic / active Waldenstrӧm Macroglobulinemia (WM).
Who cannot join
- Any serious egg allergy or prior serious adverse reaction to an influenza vaccine.
- Use of any other influenza vaccine for the 2015 to 2016 flu season.
- Women who are pregnant or plan to become pregnant in the study period.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients (SHIVERING 2)
The investigators' hypothesis is that the administration of Fluzone® High-Dose with booster to all patients with monoclonal gammopathies (irrespective of age) will lead to seroconversion rates exceeding 50% and more importantly, will reduce influenza-related morbidity, reduce interruptions in cancer therapy and may reduce disease progression at the end of the flu season
Read the detailed description
Influenza is a major cause of morbidity in the US. Patients with monoclonal gammopathies are known to have increased risk of developing influenza. Furthermore, several of the medications (such as proteasome inhibitors), commonly used to treat these tumors, are known to further increase the risk of these tumors. Seasonal influenza vaccination has been shown to reduce influenza related morbidity and is approved for routine prophylaxis in US. In 2009, Fluzone® high- dose vaccine was FDA approved in 2009 for adults aged 65 and older based on the data regarding higher rates of seroprotection (defined as hemagglutination antibody inhibition (HAI) titer of 40 or higher).
In this study, the investigators will administer Fluzone® High-Dose vaccine with a planned booster to patients with monoclonal gammopathies irrespective of age versus a standard of care control group. Primary endpoint is composite of documented influenza infection rate and disease progression (as defined by International Myeloma Working Group criteria) at the end of the flu season. Based on the background data, the investigators expect a higher rate of success in the experimental arm. As such, the investigators power for success rates of 90% and 70% in the experimental and control arms, respectively.
The investigators will also analyze several secondary endpoints including rates of influenza related morbidity, the analysis of humoral and cellular immune response to these vaccines and the rate of disease control (defined as lack of disease progression by standard international myeloma working group criteria).
- Being tested
- Fluzone High Dose Vaccine, Standard of care/Placebo
- Keywords
- influenza, multiple myeloma, Waldenstrom's macroglobulinemia
- Medical subject headings
- Influenza, Human, Multiple Myeloma, Waldenstrom Macroglobulinemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluzone High Dose VaccineBiological
Standard of care/PlaceboBiological
| Study group | Role | What they receive |
|---|---|---|
| Fluzone High Dose Vaccine then Fluzone High Dose Booster | Experimental | Fluzone High dose vaccine administered at Day 0. Fluzone High dose vaccine administered as a booster after 30 days from the initial vaccine. Receives: Biological: Fluzone High Dose Vaccine |
| Standard of Care | Active comparator | Fluzone High-Dose if age greater than or equal to 65 or Standard dose influenza vaccine if age less than 65 at day 0. Placebo administered 30 days after the initial vaccine. Receives: Biological: Standard of care/Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Failure by Primary Endpoint
Any documented flu infection during the 2015-2016 flu season or evidence of disease progression.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2015 (estimated)
- Study startSep 2015
- Primary completionOct 2017
- Study completionJun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Branagan, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02566265
- Sponsor's protocol ID
- 1507016111
- Acronym
- SHIVERING 2
- Status last verified
- Jan 2019
- First submitted
- 30 Sep 2015
- Last updated
- 30 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Branagan AR, Duffy E, Gan G, Li F, Foster C, Verma R, Zhang L, Parker TL, Seropian S, Cooper DL, Brandt D, Kortmansky J, Witt D, Ferencz TM, Dhodapkar KM, Dhodapkar MV. Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias. Blood Adv. 2021 Mar 9;5(5):1535-1539. doi: 10.1182/bloodadvances.2020003880.
PubMed 33683337
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients (SHIVERING 2)
- ClinicalTrials.gov ID
- NCT02566265
- Acronym / sponsor ID
- SHIVERING 2 / 1507016111
- Keywords
- influenza, multiple myeloma, Waldenstrom's macroglobulinemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Oct 2017 (actual)
- Study completion
- Jun 2018 (actual)
- First posted
- 2 Oct 2015 (estimated)
- Results
- Posted 30 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators' hypothesis is that the administration of Fluzone® High-Dose with booster to all patients with monoclonal gammopathies (irrespective of age) will lead to seroconversion rates exceeding 50% and more importantly, will reduce influenza-related morbidity, reduce interruptions in cancer therapy and may reduce disease progression at the end of the flu season
Detailed description
Influenza is a major cause of morbidity in the US. Patients with monoclonal gammopathies are known to have increased risk of developing influenza. Furthermore, several of the medications (such as proteasome inhibitors), commonly used to treat these tumors, are known to further increase the risk of these tumors. Seasonal influenza vaccination has been shown to reduce influenza related morbidity and is approved for routine prophylaxis in US. In 2009, Fluzone® high- dose vaccine was FDA approved in 2009 for adults aged 65 and older based on the data regarding higher rates of seroprotection (defined as hemagglutination antibody inhibition (HAI) titer of 40 or higher).
In this study, the investigators will administer Fluzone® High-Dose vaccine with a planned booster to patients with monoclonal gammopathies irrespective of age versus a standard of care control group. Primary endpoint is composite of documented influenza infection rate and disease progression (as defined by International Myeloma Working Group criteria) at the end of the flu season. Based on the background data, the investigators expect a higher rate of success in the experimental arm. As such, the investigators power for success rates of 90% and 70% in the experimental and control arms, respectively.
The investigators will also analyze several secondary endpoints including rates of influenza related morbidity, the analysis of humoral and cellular immune response to these vaccines and the rate of disease control (defined as lack of disease progression by standard international myeloma working group criteria).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluzone High Dose Vaccine then Fluzone High Dose Booster | Experimental | Biological: Fluzone High Dose VaccineFluzone High dose vaccine administered at Day 0. Fluzone High dose vaccine administered as a booster after 30 days from the initial vaccine. |
| Standard of Care | Active comparator | Biological: Standard of care/PlaceboFluzone High-Dose if age greater than or equal to 65 or Standard dose influenza vaccine if age less than 65 at day 0. Placebo administered 30 days after the initial vaccine. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Understand and voluntarily sign an informed consent form.
- Age ≥18 years at the time of signing the informed consent form.
- Diagnosis of any monoclonal gammopathy: Monoclonal Gammopathy of Undetermined Significance (MGUS), asymptomatic / active multiple myeloma, asymptomatic / active Waldenstrӧm Macroglobulinemia (WM).
Key exclusion criteria (3 listed)
- Any serious egg allergy or prior serious adverse reaction to an influenza vaccine.
- Use of any other influenza vaccine for the 2015 to 2016 flu season.
- Women who are pregnant or plan to become pregnant in the study period.
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 |
|---|---|---|
| Fluzone High Dose Vaccine | Biological | Fluzone High Dose Vaccine then Fluzone High Dose Booster |
| Standard of care/Placebo | Biological | Standard of Care |
Primary outcome
Number of Participants With Treatment Failure by Primary Endpoint
Time frame: 1 year
Any documented flu infection during the 2015-2016 flu season or evidence of disease progression.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33683337Branagan AR, Duffy E, Gan G, Li F, Foster C, Verma R, Zhang L, Parker TL, Seropian S, Cooper DL, Brandt D, Kortmansky J, Witt D, Ferencz TM, Dhodapkar KM, Dhodapkar MV. Tandem high-dose influenza vaccination is associated with more durable serologic immunity in patients with plasma cell dyscrasias. Blood Adv. 2021 Mar 9;5(5):1535-1539. doi: 10.1182/bloodadvances.2020003880.
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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.
Andrew Branagan, MD principal investigator
Yale University
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 Fluzone High Dose Vaccine in people with Influenza and Multiple Myeloma, run by Yale University at 1 site in United States.
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 3 inclusion and 3 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 30 Jan 2019. 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 United States. 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?
Yes. Results are posted in the registry (first posted 30 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment Failure by Primary Endpoint (time frame: 1 year). 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 NCT02566265, 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 30 Jan 2019.