Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients

Study Overview
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Brief Summary
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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
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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).

Official Title
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Study of High-dose Influenza Vaccine Efficacy by Repeated Dosing IN Gammopathy Patients (SHIVERING 2)

Conditions
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Influenza, Multiple Myeloma, Waldenstrom's Macroglobulinemia, Plasma Cell Disorders, MGUS

Intervention / Treatment
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* Biological: Fluzone High Dose Vaccine
* Biological: Standard of care/Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzone High Dose Vaccine then Fluzone High Dose Booster<br>Fluzone High dose vaccine administered at Day 0. Fluzone High dose vaccine administered as a booster after 30 days from the initial vaccine. | Biological: Fluzone High Dose Vaccine<br> <br> |
| Active Comparator: Standard of Care<br>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. | Biological: Standard of care/Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Failure by Primary Endpoint | Any documented flu infection during the 2015-2016 flu season or evidence of disease progression. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, multiple myeloma, Waldenstrom's macroglobulinemia