Inhibition of Anaphylaxis by Ibrutinib

This is a phase II open label study on the use of Ibrutinib on the inhibition of food-induced anaphylaxis in adults with food allergy. Ibrutinib (brand name Imbruvica) is currently FDA approved for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and Waldenstrom's macroglobulineia (WM). We propose to administer this approved drug to adults with food allergy to inhibit food allergy responses.

Study Overview

• Status: Completed
• Conditions: Food Allergy; Anaphylaxis Food
• Intervention / Treatment: Drug: Ibrutinib

Detailed Description

This is open-label study designed to determine the fewest doses and shortest length of time, from two days to up to 7 days, needed for ibrutinib to fully inhibit tests for food allergy, and to determine the length of persistence of efficacy after the drug is stopped.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Childrens Hospital of Chicago

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• History of food allergy to peanut (or tree nut).
• Male or female age ≥ 18 years.
• Positive skin prick testing and basophil activation test to the trigger food, either peanut or tree nut.
• Adequate organ and marrow function as defined below:
• leukocytes ≥ 3,000/mcL
• absolute neutrophil count ≥ 1,500/mcL
• platelets ≥ 100,000/mcl
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SPGT) within normal institutional limits
• Creatinine within normal institutional limits
• Women of child bearing potential must agree to two forms of highly effective contraception (hormonal, device, or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform the Principal Investigator and her treating physician immediately.

• A female of child bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

  • Has not undergone a hysterectomy or bilateral oophorectomy; or
  • Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
• Ability to understand and the willingness to sign a written informed consent.
• Ability to clearly understand and speak English at an 8th grade reading level. For safety reasons, subjects must speak English due to the anticipated need for clear and timely communication with investigators and the study team in emergency situations, since the investigators and study team are English speaking.

Exclusion Criteria:

• Subjects who have been on immunomodulatory therapies or oral corticosteroids within 1 month prior to study participation will be excluded, and those taking antihistamines must stop these drugs for one week prior to enrollment and must refrain from taking antihistamines during the duration of the study so as not to interfere with SPT responses.
• Subjects with symptoms not consistent with type 1 food reactions (atopic dermatitis, eosinophilic esophagitis and any other non-IgE-mediated food sensitivities) will be excluded.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ibrutinib.
• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, beta-blocker use or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Subjects on anticoagulants, anti-platelet therapy, or any other predisposition towards bleeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label Administration; Allergic subjects will be given ibrutinib 420mg daily for 2-7 doses to determine the shortest amount of time and fewest ibrutinib doses required to suppress food skin prick testing and basophil activation test reactivity.	Drug: Ibrutinib; Ibrutinib 420mg, PO once daily for 2-7 days; Other Names: Ibruvica

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Doses of Ibrutinib for Maximal Suppression of Skin Prick Test Size to Foods	The primary outcome was the number of ibrutinib doses (2, 4, or 7 doses) required to maximally suppress food skin prick reactivity to foods. All participants received 420 mg ibrutinib orally once daily for 2, 4, or 7 doses after undergoing baseline screening criteria. Skin testing to peant and tree nuts was done at baseline and repeated at each visit on days 2, 4, and 7 (corresponding to 2, 4, or 7 doses of ibrutinib).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Doses of Ibrutinib for Maximal Suppression of Basophil Reactivity	The primary outcome was to determine the fewest ibrutinib doses (2, 4, or 7 doses) required to suppress basophil reactivity (BAT). All participants received 420 mg ibrutinib orally once daily for 2, 4, or 7 doses after undergoing baseline screening criteria. Basophil activation testing was perfmored at baseline and repeated at each visit on days 2, 4, and 7 (corresponding to 2, 4, or 7 doses of ibrutinib).	7 days
Time to Recovery of Skin Test Reactivity	Another secondary outcome was to determine the timing of when skin prick testing (SPT) response to peanut or tree nuts returned to baseline compared to basophil activation test (BAT) responses. Participants underwent SPT and BAT weekly after cessation of ibrutinib therapy. SPT and BAT that were ≥80% of baseline values were considered to have "returned to baseline."	30 days

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Collaborators: Northwestern University Feinberg School of Medicine
• Investigators: Principal Investigator: Anne Marie Singh, MD, Ann & Robert H. Lurie Childrens Hospital; Principal Investigator: Bruce Bochner, MD, Northwestern Feinberg School of Medicine

Publications and helpful links

General Publications

• Dispenza MC, Pongracic JA, Singh AM, Bochner BS. Short-term ibrutinib therapy suppresses skin test responses and eliminates IgE-mediated basophil activation in adults with peanut or tree nut allergy. J Allergy Clin Immunol. 2018 May;141(5):1914-1916.e7. doi: 10.1016/j.jaci.2017.12.987. Epub 2018 Jan 31. No abstract available. Erratum In: J Allergy Clin Immunol. 2018 Oct;142(4):1374. doi: 10.1016/j.jaci.2018.08.004.

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): November 14, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity; Shock; Anaphylaxis; Tyrosine Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Ibrutinib
• Other Study ID Numbers: 2016-357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No