Influenza Vaccination for Flu Prevention in Patients With Plasma Cell Disorders

Study Overview
=================
Brief Summary
-----------------
This phase IV trial studies how well influenza vaccination works in preventing infections such as influenza in patients with plasma cell disorders. Influenza infections may theoretically support the growth of tumor cells and improving protection against influenza may improve the status of patients' plasma cell disorder. Giving influenza vaccination may reduce influenza-related complications including infections, hospitalizations, and deaths, and improve the status of plasma cell disorders.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. Demonstrate an absolute 25% increase in seroprotection, defined as hemagglutination antibody inhibition (HAI) > 40 against all strains, at week 21 in the experimental arm compared to the control arm. II. Determine correlation between HAI, predefined risk of influenza-like illness (low, moderate, high), and progression-free survival (PFS). EXPLORATORY OBJECTIVES: I. Measurement of B & T-cell subsets and flu-specific responses as a way of understanding immunosuppression in this patient population, correlating with influenza-like illness. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive trivalent influenza vaccine intramuscularly (IM) at weeks 1, 9, and 17, and pneumococcal 13-valent conjugate vaccine IM at week 5 in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive trivalent influenza vaccine IM at week 1 and pneumococcal 13-valent conjugate vaccine IM at week 5 in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 4 weeks and then periodically for 2 years.

Official Title
-----------------
Influenza Vaccination in Plasma Cell Dyscrasias

Conditions
-----------------
Plasma Cell Neoplasm

Intervention / Treatment
-----------------
* Biological: Pneumococcal 13-valent Conjugate Vaccine
* Biological: Trivalent Influenza Vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must have a plasma cell dyscrasia that fits in the International Myeloma Working Group (IMWG) diagnostic criteria. Both men and women of all races and ethnic groups are eligible for this study. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3 (Karnofsky ≥ 30%) is required for eligibility. Patient must be eligible to receive standard of care influenza vaccination. If the patient has a history of egg allergy with symptoms more severe than urticaria, e.g. angioedema, respiratory distress, lightheadedness, or recurrent emesis, they remain eligible to receive influenza vaccination but must receive the vaccine in a facility able to recognize and manage severe allergic reactions. Persons who are able to eat lightly cooked egg (e.g., scrambled egg) without reaction are unlikely to be allergic, although egg-allergic persons might tolerate egg in baked products. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Patients who have already received the seasonal influenza vaccine in the current season. History of Guillain-Barré syndrome. Patients with a previous severe allergic reaction to influenza vaccination or pneumococcal 13-valent conjugate vaccine (PCV13). Expected survival < 9 months. Prisoners.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (trivalent influenza vaccine, Prevnar)<br>Patients receive trivalent influenza vaccine IM at weeks 1, 9, and 17, and pneumococcal 13-valent conjugate vaccine IM at week 5 in the absence of disease progression or unacceptable toxicity. | Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Given IM<br>* Other names: Prevnar 13;Biological: Trivalent Influenza Vaccine<br>* Given IM<br>* Other names: TIV;|
| Experimental: Arm II (trivalent influenza vaccine, Prevnar)<br>Patients receive trivalent influenza vaccine IM at week 1 and pneumococcal 13-valent conjugate vaccine IM at week 5 in the absence of disease progression or unacceptable toxicity. | Biological: Pneumococcal 13-valent Conjugate Vaccine<br>* Given IM<br>* Other names: Prevnar 13;Biological: Trivalent Influenza Vaccine<br>* Given IM<br>* Other names: TIV;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemagglutination antibody inhibition (HAI) from baseline | Assess change in HAI in blood from baseline compared to week 21 | 21 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression (TTP) | Time to progression is defined as the time from last treatment until progression. Patients who have died without evidence of progression are censored in the TTP analysis at the time of death and patients who are alive without progression are censored at the last disease assessment. | From last treatment until progression, assessed up to 2 years | 
| Progression free survival (PFS) | Defined as the time from last treatment to the disease progression or death from any cause. Patients who have not progressed or died are censored at the date last known progression-free. Patients with no on-study assessment will be censored at the time of registration. | From last treatment to the disease progression or death from any cause, assessed up to 2 years | 
| Overall survival (OS) | OS is defined as the time from randomization to death. Alive patients are censored at the date last known alive. | From randomization to death, assessed up to 2 years |