Influenza Vaccination for Flu Prevention in Patients With Plasma Cell Disorders

• ClinicalTrials.gov Identifier: NCT04080531
• Recruitment Status: Active, not recruiting
• First Posted: September 6, 2019
• Last Update Posted: February 8, 2023
• Sponsor: Emory University
• Collaborator: Sanofi
• Information provided by (Responsible Party): Craig Hofmeister, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Plasma Cell Neoplasm	Biological: Pneumococcal 13-valent Conjugate Vaccine; Biological: Trivalent Influenza Vaccine	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 165 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Influenza Vaccination in Plasma Cell Dyscrasias
• Actual Study Start Date: October 18, 2019
• Estimated Primary Completion Date: October 31, 2023
• Estimated Study Completion Date: October 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I (trivalent influenza vaccine, Prevnar); 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; Given IM; Other Names: PCV13; Prevnar 13; Biological: Trivalent Influenza Vaccine; Given IM; Other Names: Flu shot; Flu vaccination; Fluzone; Fluzone HD; Fluzone High-dose; Influenza Vaccine; Influenza Virus Vaccine, Trivalent, Types A and B; TIV
Experimental: Arm II (trivalent influenza vaccine, Prevnar); 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; Given IM; Other Names: PCV13; Prevnar 13; Biological: Trivalent Influenza Vaccine; Given IM; Other Names: Flu shot; Flu vaccination; Fluzone; Fluzone HD; Fluzone High-dose; Influenza Vaccine; Influenza Virus Vaccine, Trivalent, Types A and B; TIV

Outcome Measures

Primary Outcome Measures :

1. Change in hemagglutination antibody inhibition (HAI) from baseline [ Time Frame: 21 weeks ]
   Assess change in HAI in blood from baseline compared to week 21

Secondary Outcome Measures :

1. Time to progression (TTP) [ Time Frame: From last treatment until progression, assessed up to 2 years ]
   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.
2. Progression free survival (PFS) [ Time Frame: From last treatment to the disease progression or death from any cause, assessed up to 2 years ]
   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.
3. Overall survival (OS) [ Time Frame: From randomization to death, assessed up to 2 years ]
   OS is defined as the time from randomization to death. Alive patients are censored at the date last known alive.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Georgia

Emory University Hospital Midtown

Atlanta, Georgia, United States, 30308

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Sanofi

Investigators

• Principal Investigator: Craig Hofmeister, MD, MPH; Emory University

More Information

• Responsible Party: Craig Hofmeister, Principal Investigator, Emory University
• ClinicalTrials.gov Identifier: NCT04080531
• Other Study ID Numbers: IRB00111721; NCI-2019-03734 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); Winship4709-19 ( Other Identifier: Emory University Hospital/Winship Cancer Institute )
• First Posted: September 6, 2019
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms, Plasma Cell; Multiple Myeloma; Plasmacytoma; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs