BRCA1/2 Flu Vaccine

NCT04499534 | Active Not Recruiting

• 2 other identifiers: UPCC 11119834194
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate immune function in BRCA1/2 mutation carriers without cancer, specifically to determine whether immune function in healthy individuals with germline loss of function BRCA1/2 mutations, impacts overall immune health and fitness.

Conditions

BRCA1 Mutation; BRCA2 Mutation

Outcome Measures

Primary Outcomes (1)

• To evaluate immune function in female BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination

  Analysis of the primary objective will depend on determination of the strain-specific neutralizing antibody titer change from day 0 to the last study visit, performed as the standard assay as described by the World Health Organization (WHO).

  2 years

Secondary Outcomes (2)

• Exploratory analysis- phenotypic evaluation of B cell

  2 years

• Exploratory analysis - transcriptional evaluation

  2 years

Interventions

Seasonal influenza vaccine BIOLOGICAL

To evaluate immune function in BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients 25 years and older, seen at Cancer Risk Evaluation Program (CREP) in the Perelman Center for Advanced Medicine with BRCA1 or BRCA2 mutation.

You may qualify if:

• Males and females
• Over age 25
• BRCA1 or BRCA2 pathogenic or likely pathogenic mutation
• No personal cancer history apart from non melanoma skin cancer, localized thyroid cancer, in situ cancers of any type
• Participants must sign the informed consent form

You may not qualify if:

• Are allergic to influenza vaccination
• Have received influenza vaccination within the past 6 months
• Require prednisone, methotrexate, or other immunosuppressing medications
• Have HIV infection
• Have a history of solid organ tumor or bone marrow transplant
• Require combination immunotherapy;
• Are on other studies requiring blood draws that might exceed 450 mL total during the period of the influenza vaccine study

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (9)

• Mouw KW, Goldberg MS, Konstantinopoulos PA, D'Andrea AD. DNA Damage and Repair Biomarkers of Immunotherapy Response. Cancer Discov. 2017 Jul;7(7):675-693. doi: 10.1158/2159-8290.CD-17-0226. Epub 2017 Jun 19.

  PMID: 28630051 BACKGROUND

• Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.

  PMID: 25594173 BACKGROUND

• Casanova JL, Abel L, Quintana-Murci L. Immunology taught by human genetics. Cold Spring Harb Symp Quant Biol. 2013;78:157-72. doi: 10.1101/sqb.2013.78.019968. Epub 2013 Oct 3.

  PMID: 24092470 BACKGROUND

• Lucas CL, Lenardo MJ. Identifying genetic determinants of autoimmunity and immune dysregulation. Curr Opin Immunol. 2015 Dec;37:28-33. doi: 10.1016/j.coi.2015.09.001. Epub 2015 Oct 2.

  PMID: 26433354 BACKGROUND

• Mak TW, Hakem A, McPherson JP, Shehabeldin A, Zablocki E, Migon E, Duncan GS, Bouchard D, Wakeham A, Cheung A, Karaskova J, Sarosi I, Squire J, Marth J, Hakem R. Brca1 required for T cell lineage development but not TCR loci rearrangement. Nat Immunol. 2000 Jul;1(1):77-82. doi: 10.1038/76950.

  PMID: 10881179 BACKGROUND

• Cheung AM, Hande MP, Jalali F, Tsao MS, Skinnider B, Hirao A, McPherson JP, Karaskova J, Suzuki A, Wakeham A, You-Ten A, Elia A, Squire J, Bristow R, Hakem R, Mak TW. Loss of Brca2 and p53 synergistically promotes genomic instability and deregulation of T-cell apoptosis. Cancer Res. 2002 Nov 1;62(21):6194-204.

  PMID: 12414647 BACKGROUND

• Centers for Disease Control and Prevention (CDC). Estimates of deaths associated with seasonal influenza --- United States, 1976-2007. MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62.

  PMID: 20798667 BACKGROUND

• Herati RS, Reuter MA, Dolfi DV, Mansfield KD, Aung H, Badwan OZ, Kurupati RK, Kannan S, Ertl H, Schmader KE, Betts MR, Canaday DH, Wherry EJ. Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults. J Immunol. 2014 Oct 1;193(7):3528-37. doi: 10.4049/jimmunol.1302503. Epub 2014 Aug 29.

  PMID: 25172499 BACKGROUND

• Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000 Dec 4;192(11):1553-62. doi: 10.1084/jem.192.11.1553.

  PMID: 11104798 BACKGROUND

Study Officials

• Susan Domchek, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2020
• First Posted: August 5, 2020
• Study Start: October 28, 2019
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: October 6, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)