BRCA1/2 Flu Vaccine

BRCA1 Mutation Clinical Trial

Official title:

Influenza Vaccine Study in BRCA1 or BRCA2 Carriers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04499534
• Other study ID #: UPCC 11119
• Secondary ID: 834194
• Status: Recruiting
• Start date: October 28, 2019
• Est. completion date: June 2024

Study information

• Verified date: October 2023
• Source: Abramson Cancer Center at Penn Medicine
• Contact: Susan Domchek, MD
• Phone: 215-615-3360
• Email: susan.domchek[@]pennmedicine.upenn.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• BRCA1 Mutation
• BRCA2 Mutation

Intervention

Biological:
• Seasonal influenza vaccine
To evaluate immune function in BRCA1/2 mutation carriers without cancer following seasonal influenza vaccination

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Abramson Cancer Center at Penn Medicine

Country where clinical trial is conducted

United States, 

References & Publications (9)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Exploratory analysis- phenotypic evaluation of B cell	Phenotypic evaluation of B and T cell responses to vaccine at each timepoint. Phenotypic analysis involves flow cytometry on peripheral blood mononuclear cells (PBMC) from all subjects (10 mL blood per subject).	2 years
Secondary	Exploratory analysis - transcriptional evaluation	Transcriptional evaluation of B and T cell responses to vaccine on day 7-10 timepoint. Transcriptional analyses including quantitative real-time PCR (RT-qPCR) and RNA sequencing (RNAseq) may be performed on a subset of the study subjects on the day 7-10 time point.	2 years