Anaphylaxis Food, Food Allergy
Conditions
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.
Interventions
DRUGIbrutinib
Ibrutinib 420mg, PO once daily for 2-7 days
Sponsors
Northwestern University Feinberg School of Medicine
Ann & Robert H Lurie Children's Hospital of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Doses of Ibrutinib for Maximal Suppression of Skin Prick Test Size to Foods | 7 days | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Doses of Ibrutinib for Maximal Suppression of Basophil Reactivity | 7 days | 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). |
| Time to Recovery of Skin Test Reactivity | 30 days | 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. |
Countries
United States
Participant flow
Pre-assignment details
Participants were excluded if baseline skin prick tests to peanut/tree nuts were all negative.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants received ibrutinib after undergoing baseline screening criteria. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 32.8 years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
| Skin prick test to peanut and/or tree nuts | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
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).
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibrutinib | Number of Doses of Ibrutinib for Maximal Suppression of Skin Prick Test Size to Foods | 2 doses | Standard Deviation 0 |
p-value: <0.0001Wilcoxon (Mann-Whitney)
Secondary
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).
Time frame: 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibrutinib | Number of Doses of Ibrutinib for Maximal Suppression of Basophil Reactivity | 2 doses | Standard Deviation 0 |
p-value: <0.001ANOVA
Secondary
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.
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibrutinib | Time to Recovery of Skin Test Reactivity | 1.24 weeks | Standard Deviation 0.6633 |