Clinical trial NCT03149315: Inhibition of Anaphylaxis by Ibrutinib
Official title: Inhibition of Anaphylaxis by Ibrutinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Allergy
Anaphylaxis Food
Lead sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
Sponsor class: OTHER
Collaborators: name: Northwestern University Feinberg School of Medicine
First posted: 2017-05-11
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Doses of Ibrutinib for Maximal Suppression of Skin Prick Test Size to Foods
timeFrame: 7 days
Secondary outcomes:
measure: Number of Doses of Ibrutinib for Maximal Suppression of Basophil Reactivity
timeFrame: 7 days
measure: Time to Recovery of Skin Test Reactivity
timeFrame: 30 days
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Childrens Hospital of Chicago
state: Illinois
Study officials:
affiliation: Ann & Robert H. Lurie Childrens Hospital
name: Anne Marie Singh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern Feinberg School of Medicine
name: Bruce Bochner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.