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

Yale University

Status and phase: Completed; Phase 2

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

Treatments: Biological: Standard of care/Placebo; Biological: Fluzone High Dose Vaccine

Study type: Interventional

Funder types: Other

Identifiers

NCT02566265

1507016111

Details and patient eligibility

About

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

Full 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).

Enrollment: 122 patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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122 participants in 2 patient groups

Fluzone High Dose Vaccine then Fluzone High Dose Booster

Experimental group

Description:

Fluzone High dose vaccine administered at Day 0. Fluzone High dose vaccine administered as a booster after 30 days from the initial vaccine.

Treatment:

Biological: Fluzone High Dose Vaccine

Standard of Care

Active Comparator group

Description:

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.

Treatment:

Biological: Standard of care/Placebo