Clinical trial NCT02566265: Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients
Official title: Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients (SHIVERING 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Multiple Myeloma
Waldenstrom's Macroglobulinemia
Plasma Cell Disorders
MGUS
Keywords: influenza
multiple myeloma
Waldenstrom's macroglobulinemia
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2015-10-02
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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).

Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of Participants With Treatment Failure by Primary Endpoint
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Andrew Branagan, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.