Influenza, MGUS, Multiple Myeloma, Plasma Cell Disorders, Waldenstrom's Macroglobulinemia
Conditions
Keywords
influenza, multiple myeloma, Waldenstrom's macroglobulinemia
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).
Interventions
BIOLOGICALFluzone High Dose Vaccine
BIOLOGICALStandard of care/Placebo
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Failure by Primary Endpoint | 1 year | Any documented flu infection during the 2015-2016 flu season or evidence of disease progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluzone High Dose Vaccine Then Fluzone High Dose Booster Fluzone High dose vaccine administered at Day 0. Fluzone High dose vaccine administered as a booster after 30 days from the initial vaccine.
Fluzone High Dose Vaccine | 81 |
| Standard of Care 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.
Standard of care/Placebo | 41 |
| Total | 122 |
Baseline characteristics
| Characteristic | Fluzone High Dose Vaccine Then Fluzone High Dose Booster | Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 67 years | 66 years | 67 years |
| Detailed Diagnosis Asymptomatic Myeloma | 8 Participants | 1 Participants | 9 Participants |
| Detailed Diagnosis Asymptomatic WM | 0 Participants | 3 Participants | 3 Participants |
| Detailed Diagnosis MGUS | 11 Participants | 4 Participants | 15 Participants |
| Detailed Diagnosis Multiple Myeloma | 53 Participants | 28 Participants | 81 Participants |
| Detailed Diagnosis Other | 3 Participants | 1 Participants | 4 Participants |
| Detailed Diagnosis WM | 6 Participants | 4 Participants | 10 Participants |
| Disease Stage Advanced | 64 Participants | 32 Participants | 96 Participants |
| Disease Stage Early | 17 Participants | 9 Participants | 26 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Region of Enrollment United States | 81 Participants | 41 Participants | 122 Participants |
| Sex: Female, Male Female | 42 Participants | 18 Participants | 60 Participants |
| Sex: Female, Male Male | 39 Participants | 23 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 81 | 2 / 41 |
| other Total, other adverse events | 0 / 81 | 0 / 41 |
| serious Total, serious adverse events | 8 / 81 | 1 / 41 |
Outcome results
Primary
Number of Participants With Treatment Failure by Primary Endpoint
Any documented flu infection during the 2015-2016 flu season or evidence of disease progression.
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fluzone High Dose Vaccine Then Fluzone High Dose Booster | Number of Participants With Treatment Failure by Primary Endpoint | 26 Participants |
| Standard of Care | Number of Participants With Treatment Failure by Primary Endpoint | 13 Participants |